Objective Regeneration of corticospinal tract (CST) axons after spinal cord injury (SCI) is a key element in rebuilding neuronal connections to restore voluntary motor function. However, it remains challenging owing to limited effective interventions. This study adopted a modified transcranial optogenetic technique to stimulate CST axon regeneration into the injury site of completely transected SCI and explore the underlying molecular mechanisms.
Methods A novel optogenetic light emitting diode (LED) device was used to stimulate the brain motor cortex in channelrhodopsin-2–yellow fluorescent protein (ChR2-YFP) transgenic mice to observe the regeneration of CST axons in the injury site of a complete SCI. The LED device was also used In vitro to stimulate the motor cortex slices of the transgenic mouse brain for observing the outgrowth of their neurites.
Results After transcranial optogenetic stimulation, the pyramidal neurons of bilateral cerebral motor cortices, in ChR2-YFP transgenic mice were activated, CST axons regenerated into the injury site of the spinal cord, and the motor function of the paralyzed hindlimbs improved. Proteomic analysis revealed that CST axon regeneration was associated with the activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in the cerebral motor cortices. In vitro LED blue light illumination enhanced the outgrowth of neurites from the brain slices of transgenic mice. Treatment with a JAK2/STAT3 inhibitor led to a significant attenuation of neurite outgrowth.
Conclusion The modified transcranial optogenetic technique stimulated bilateral motor cortices, in the brains of ChR2-YFP transgenic mice. It increased the excitability of pyramidal neurons in the motor cortices, and promoted CST axon regeneration by activating the JAK2/STAT3 pathway, repairing complete SCI.
Citations
Citations to this article as recorded by
Frontier Integration in Spinal Cord Injury Repair: Engineering-Driven Mechanistic Exploration and a New Paradigm for Clinical Translation Mi Zhou, Xue Yao, Boya Huang, Jie Ren, Haiwen Feng, Shiqing Feng Engineering.2026; 60: 310. CrossRef
Multimodal electroconductive PLGA-based scaffold orchestrates neuroprotection and regeneration following severe spinal cord injury So-Yeon Park, Gyubin Kim, Yanting Liu, Ji-Won Jung, Jeoung Eun Lee, Jun-Kyu Lee, Dong-Hee Kim, Juwon Youn, Seung-Woon Baek, Dong Ryul Lee, Dong-Youn Hwang, Tae-Keun Ahn, Da-Seul Kim, Inbo Han, Dong Keun Han Journal of Nanobiotechnology.2026;[Epub] CrossRef
Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han International Journal of Molecular Sciences.2026; 27(4): 2079. CrossRef
NanoScript-Enabled Nonviral Transient Repression of Phosphatase and Tensin Homolog for Axonal Regeneration and Central Nervous System Injury Repair Brandon Conklin, Yanting Liu, Sarah Nevins, Byeong-Gwan Song, Sy-Tsong Dean Chueng, Qiu Xiaowen, Sungyun Kim, Heyin Cheung, Seong Bae An, JongMin Lee, Bong Geun Chung, Wise Young, Dongming Sun, Hiroshi Sugiyama, Inbo Han, Ki-Bum Lee ACS Nano.2026; 20(8): 6582. CrossRef
3D bioprinted multifunctional GelMA/TMP scaffold integrated with neural stem cell-derived extracellular vesicles and neural progenitor cells for spinal cord injury repair Yanting Liu, Gyubin Kim, Jun Yong Kim, Jeong Min Park, Duck Hyun Song, Jun-Kyu Lee, So-Yeon Park, Inbo Han, Dong Keun Han Journal of Tissue Engineering.2026;[Epub] CrossRef
Spinal cord extracellular matrix hydrogel enhances organoid maturation and functional regeneration after spinal cord injury Junghoon Kim, Songzi Zhang, Joon-Hyuk Jung, Mi-Jeong Lee, Inbo Han, Seung-Woo Cho Materials Today Bio.2026; 38: 103168. CrossRef
Injectable Poloxamer and Hyaluronic Acid Hydrogel for Sustained Co-Delivery of Dexamethasone and Lidocaine Ameliorates Neuropathic Pain Yanting Liu, Seungwoon Baik, Trung Nhan Vo, Songzi Zhang, Boram Kim, Tae-Keun Ahn, Inbo Han, Dong Keun Han Biomaterials Research.2026;[Epub] CrossRef
A Commentary on “Transcranial Optogenetic Stimulation Promotes Corticospinal Tract Axon Regeneration to Repair Spinal Cord Injury by Activating the JAK2/STAT3 Pathway” Wu Xue, Anyuan Dai, Qinyi Liu Neurospine.2025; 22(2): 329. CrossRef
From the Editor-in-Chief: Featured Articles in the June 2025 Issue Inbo Han Neurospine.2025; 22(2): 309. CrossRef
Potential Pharmacologic Treatments in Spinal Cord Injury: A Narrative Review Kyeong Deuk An, Chan Yang Noh, Junsoo Jang, Woon Tak Yuh, Il Choi Korean Journal of Neurotrauma.2025; 21(4): 237. CrossRef
Objective Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms.
Methods By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway.
Results In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway.
Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.
Citations
Citations to this article as recorded by
Multimodal electroconductive PLGA-based scaffold orchestrates neuroprotection and regeneration following severe spinal cord injury So-Yeon Park, Gyubin Kim, Yanting Liu, Ji-Won Jung, Jeoung Eun Lee, Jun-Kyu Lee, Dong-Hee Kim, Juwon Youn, Seung-Woon Baek, Dong Ryul Lee, Dong-Youn Hwang, Tae-Keun Ahn, Da-Seul Kim, Inbo Han, Dong Keun Han Journal of Nanobiotechnology.2026;[Epub] CrossRef
Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han International Journal of Molecular Sciences.2026; 27(4): 2079. CrossRef
3D bioprinted multifunctional GelMA/TMP scaffold integrated with neural stem cell-derived extracellular vesicles and neural progenitor cells for spinal cord injury repair Yanting Liu, Gyubin Kim, Jun Yong Kim, Jeong Min Park, Duck Hyun Song, Jun-Kyu Lee, So-Yeon Park, Inbo Han, Dong Keun Han Journal of Tissue Engineering.2026;[Epub] CrossRef
Spinal cord extracellular matrix hydrogel enhances organoid maturation and functional regeneration after spinal cord injury Junghoon Kim, Songzi Zhang, Joon-Hyuk Jung, Mi-Jeong Lee, Inbo Han, Seung-Woo Cho Materials Today Bio.2026; 38: 103168. CrossRef
Multifunctional Nanozyme Hydrogel for Oxidative Stress Scavenging and Mitophagy Activation in Spinal Cord Injury Repair Zhen Dai, Hui Lu, Yanfeng Yang, Huicong Feng, Yijia Zhang, Zuqiang Shi, Ensi Liu, Haosen Zhao, Xifan Mei, Yansong Wang ACS Applied Materials & Interfaces.2026; 18(20): 28449. CrossRef
Machine learning-assisted prediction of PANoptosis-related molecular targets and precise screening of neuroprotective drugs for spinal cord injury Dongmei Wang, Rui Wang, Huangmei Liao, Feiyang Lu, Zepeng Guo, Ruijun Xu, Aini Chen, Zhen Niu, Yusen Ou, Ge Li Experimental Neurology.2026; 404: 115884. CrossRef
LncRNA NORAD Promotes Spinal Cord Injury via miR-22-3p/PTEN Axis to Regulate Oxidative Stress and Inflammation in Neuronal Cells Chenming Zhang, Lin Chen, Yue Pan, Shiwei Yu, Qingyi Wang, Yongfu Chen, Haitao Xu, Yuanyuan Zhang Global Spine Journal.2026;[Epub] CrossRef
Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury Lahanya Guha, Divya Goyal, Nidhi Singh, Mamidi Teena, Inbo Han, Hemant Kumar Molecular Neurobiology.2025; 62(10): 13763. CrossRef
Potential Pharmacologic Treatments in Spinal Cord Injury: A Narrative Review Kyeong Deuk An, Chan Yang Noh, Junsoo Jang, Woon Tak Yuh, Il Choi Korean Journal of Neurotrauma.2025; 21(4): 237. CrossRef
Objective Spinal cord injury (SCI) leads to severe motor and sensory deficits, with limited treatment options. This study investigates how methylprednisolone-loaded nanoparticles (MP-NPs) modulate SCI repair by targeting solute carrier family 16 member 3 (SLC16A3) and reshaping the macrophage-inflammatory microenvironment.
Methods Transcriptome data were analyzed to identify differentially expressed genes (DEGs) associated with SCI. Immune infiltration and WGCNA (Weighted Gene Co-expression Network Analysis) identified genes linked to M2 macrophage polarization, pinpointing SLC16A3 as a key regulatory factor. MP-NPs were synthesized, characterized, and tested for their effects on macrophage polarization, neuronal protection, and SCI recovery in rats.
Results We identified 612 DEGs related to inflammation and immune response in SCI. SLC16A3, upregulated in SCI, was downregulated by MP-NPs. In vitro, MP-NPs promoted M2 macrophage polarization, enhanced neuronal survival, and supported neural stem cell differentiation. In vivo, MP-NPs significantly improved motor recovery, reduced inflammation, and facilitated neural repair in SCI rats.
Conclusion MP-NPs downregulate SLC16A3 and modulate the macrophage-inflammatory environment, promoting neural repair and functional recovery in SCI, offering a promising therapeutic strategy.
Citations
Citations to this article as recorded by
Multimodal electroconductive PLGA-based scaffold orchestrates neuroprotection and regeneration following severe spinal cord injury So-Yeon Park, Gyubin Kim, Yanting Liu, Ji-Won Jung, Jeoung Eun Lee, Jun-Kyu Lee, Dong-Hee Kim, Juwon Youn, Seung-Woon Baek, Dong Ryul Lee, Dong-Youn Hwang, Tae-Keun Ahn, Da-Seul Kim, Inbo Han, Dong Keun Han Journal of Nanobiotechnology.2026;[Epub] CrossRef
NanoScript-Enabled Nonviral Transient Repression of Phosphatase and Tensin Homolog for Axonal Regeneration and Central Nervous System Injury Repair Brandon Conklin, Yanting Liu, Sarah Nevins, Byeong-Gwan Song, Sy-Tsong Dean Chueng, Qiu Xiaowen, Sungyun Kim, Heyin Cheung, Seong Bae An, JongMin Lee, Bong Geun Chung, Wise Young, Dongming Sun, Hiroshi Sugiyama, Inbo Han, Ki-Bum Lee ACS Nano.2026; 20(8): 6582. CrossRef
ROS-scavenging and oxygen-generating MgMn-LDH integrated smart injectable hydrogel for microenvironment-reprogrammable spinal cord injury repair Lian Ren, Xiaobin Zhou, Longbao Feng, Guodong Sun Materials Advances.2026; 7(7): 3586. CrossRef
Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han International Journal of Molecular Sciences.2026; 27(4): 2079. CrossRef
3D bioprinted multifunctional GelMA/TMP scaffold integrated with neural stem cell-derived extracellular vesicles and neural progenitor cells for spinal cord injury repair Yanting Liu, Gyubin Kim, Jun Yong Kim, Jeong Min Park, Duck Hyun Song, Jun-Kyu Lee, So-Yeon Park, Inbo Han, Dong Keun Han Journal of Tissue Engineering.2026;[Epub] CrossRef
Spinal cord extracellular matrix hydrogel enhances organoid maturation and functional regeneration after spinal cord injury Junghoon Kim, Songzi Zhang, Joon-Hyuk Jung, Mi-Jeong Lee, Inbo Han, Seung-Woo Cho Materials Today Bio.2026; 38: 103168. CrossRef
Injectable Poloxamer and Hyaluronic Acid Hydrogel for Sustained Co-Delivery of Dexamethasone and Lidocaine Ameliorates Neuropathic Pain Yanting Liu, Seungwoon Baik, Trung Nhan Vo, Songzi Zhang, Boram Kim, Tae-Keun Ahn, Inbo Han, Dong Keun Han Biomaterials Research.2026;[Epub] CrossRef
Potential Pharmacologic Treatments in Spinal Cord Injury: A Narrative Review Kyeong Deuk An, Chan Yang Noh, Junsoo Jang, Woon Tak Yuh, Il Choi Korean Journal of Neurotrauma.2025; 21(4): 237. CrossRef
Objective Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date.
Methods Computational docking and molecular dynamics simulation studies were performed to assess myricetin’s potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin.
Results Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo.
Conclusion In summary, our findings underscore myricetin’s potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway.
Citations
Citations to this article as recorded by
Multimodal electroconductive PLGA-based scaffold orchestrates neuroprotection and regeneration following severe spinal cord injury So-Yeon Park, Gyubin Kim, Yanting Liu, Ji-Won Jung, Jeoung Eun Lee, Jun-Kyu Lee, Dong-Hee Kim, Juwon Youn, Seung-Woon Baek, Dong Ryul Lee, Dong-Youn Hwang, Tae-Keun Ahn, Da-Seul Kim, Inbo Han, Dong Keun Han Journal of Nanobiotechnology.2026;[Epub] CrossRef
NanoScript-Enabled Nonviral Transient Repression of Phosphatase and Tensin Homolog for Axonal Regeneration and Central Nervous System Injury Repair Brandon Conklin, Yanting Liu, Sarah Nevins, Byeong-Gwan Song, Sy-Tsong Dean Chueng, Qiu Xiaowen, Sungyun Kim, Heyin Cheung, Seong Bae An, JongMin Lee, Bong Geun Chung, Wise Young, Dongming Sun, Hiroshi Sugiyama, Inbo Han, Ki-Bum Lee ACS Nano.2026; 20(8): 6582. CrossRef
Photobiomodulation Therapy with Zinc Oxide/Pheophorbide-a Nanoflakes Enhances Neurovascular Repair in Spinal Cord Injury Evidenced Using Photoacoustic Imaging Santimoy Sen, Prathamesh Mahadev Patil, Nidhi Parihar, Sweta Saswati Das, Ankita Damaleshwar Saha, Deepak B. Pemmaraju ACS Applied Bio Materials.2026; 9(6): 2876. CrossRef
Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han International Journal of Molecular Sciences.2026; 27(4): 2079. CrossRef
3D bioprinted multifunctional GelMA/TMP scaffold integrated with neural stem cell-derived extracellular vesicles and neural progenitor cells for spinal cord injury repair Yanting Liu, Gyubin Kim, Jun Yong Kim, Jeong Min Park, Duck Hyun Song, Jun-Kyu Lee, So-Yeon Park, Inbo Han, Dong Keun Han Journal of Tissue Engineering.2026;[Epub] CrossRef
Theranostic CuS/ALA Nanoprobes Modulate Drug Efflux Pumps and Synergize the Photoacoustics-Guided Photothermal Breast Cancer Therapy Nidhi Parihar, Prathamesh Mahadev Patil, Santimoy Sen, Amanda Marak, Deepak Bharadwaj Pemmaraju ACS Applied Materials & Interfaces.2026; 18(17): 24104. CrossRef
Integrative QSAR strategies for hexokinase 2 (HK2) targeting: combining ligand-based, structure-based, and AI-enabled drug discovery Rudradip Das In Silico Research in Biomedicine.2026; 2: 100482. CrossRef
Research Progress of Flavonoids in Spinal Cord Injury: Therapeutic Mechanisms and Drug Delivery Strategies Shizhe Li, Shutao Gao, Yukun Hu, Jingsheng Feng, Weibin Sheng Phytotherapy Research.2025; 39(6): 2555. CrossRef
Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury Lahanya Guha, Divya Goyal, Nidhi Singh, Mamidi Teena, Inbo Han, Hemant Kumar Molecular Neurobiology.2025; 62(10): 13763. CrossRef
Exploring the Neuroprotective Potentials of Flavonoid Metabolites in Syzygium aromaticum: A Review with in-silico Insight to Therapeutic Potential Ekom Etukudo, Ibe Usman, Augustine Oviosun, Vivian Ojiakor, Wusa Makena, Elna Owembabazi, Patrick Aja, Bives Mutume Nzanzu Vivalya, Victor Archibong, Emeka Anyanwu Journal of Experimental Pharmacology.2025; Volume 17: 587. CrossRef
Objective The study aimed to investigate the role of N6-methyladenosine (m6A) modification in spinal cord injury (SCI) and its underlying mechanism, focusing on the interplay between m6A methyltransferase-like 3 (METTL3), miR-30c, and autophagy-related proteins.
Methods An SCI model was established in rats, and changes in autophagy-related proteins, m6A methylation levels, and miR-30c levels were analyzed. Hydrogen peroxide (H2O2)-stimulated spinal cord neuron cells (SCNCs) were used to assess the impact of METTL3 overexpression. The effects of STM2457, an antagonist of METTL3, were evaluated on cell viability, apoptosis, and autophagy markers in H2O2-stimulated SCNCs.
Results In the SCI model, decreased levels of autophagy markers and increased m6A methylation, miR-30c levels, and METTL3 were observed. Overexpression of METTL3 in SCNCs led to reduced cell viability, increased apoptosis, and suppressed autophagy. Conversely, co-overexpression of autophagy-related protein 5 (ATG5) or miR-30c inhibition reversed these effects. Knocking out METTL3 yielded opposite results. STM2457 treatment improved cell viability, reduced apoptosis, and upregulated autophagy markers in SCNCs, which also enhanced functional recovery in rats as measured by the Basso-Beattie-Bresnahan score and inclined plate test.
Conclusion STM2457 alleviated SCI by suppressing METTL3-mediated m6A modification of miR-30c, which in turn induces ATG5-mediated autophagy. This study provides insights into the role of m6A modification in SCI and suggests a potential therapeutic approach through targeting METTL3.
Citations
Citations to this article as recorded by
Multimodal electroconductive PLGA-based scaffold orchestrates neuroprotection and regeneration following severe spinal cord injury So-Yeon Park, Gyubin Kim, Yanting Liu, Ji-Won Jung, Jeoung Eun Lee, Jun-Kyu Lee, Dong-Hee Kim, Juwon Youn, Seung-Woon Baek, Dong Ryul Lee, Dong-Youn Hwang, Tae-Keun Ahn, Da-Seul Kim, Inbo Han, Dong Keun Han Journal of Nanobiotechnology.2026;[Epub] CrossRef
YTHDF2 promotes arsenic carcinogenesis through m6A-dependent SMAD7 decay and PRR5 escape from decay Qian Zhang, Jin Man, Jingsilin Cai, Tianhe Zhao, Zunzhen Zhang International Journal of Biological Macromolecules.2026; 348: 150816. CrossRef
NanoScript-Enabled Nonviral Transient Repression of Phosphatase and Tensin Homolog for Axonal Regeneration and Central Nervous System Injury Repair Brandon Conklin, Yanting Liu, Sarah Nevins, Byeong-Gwan Song, Sy-Tsong Dean Chueng, Qiu Xiaowen, Sungyun Kim, Heyin Cheung, Seong Bae An, JongMin Lee, Bong Geun Chung, Wise Young, Dongming Sun, Hiroshi Sugiyama, Inbo Han, Ki-Bum Lee ACS Nano.2026; 20(8): 6582. CrossRef
Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han International Journal of Molecular Sciences.2026; 27(4): 2079. CrossRef
3D bioprinted multifunctional GelMA/TMP scaffold integrated with neural stem cell-derived extracellular vesicles and neural progenitor cells for spinal cord injury repair Yanting Liu, Gyubin Kim, Jun Yong Kim, Jeong Min Park, Duck Hyun Song, Jun-Kyu Lee, So-Yeon Park, Inbo Han, Dong Keun Han Journal of Tissue Engineering.2026;[Epub] CrossRef
Comprehensive analysis of m6A RNA methylation regulators and the immune microenvironment in spinal cord injury Xiaoqin Liu, Jiating Hu, Guodong Shi, Wenxia Zhu, Qiao Hao Frontiers in Neurology.2026;[Epub] CrossRef
Injectable Poloxamer and Hyaluronic Acid Hydrogel for Sustained Co-Delivery of Dexamethasone and Lidocaine Ameliorates Neuropathic Pain Yanting Liu, Seungwoon Baik, Trung Nhan Vo, Songzi Zhang, Boram Kim, Tae-Keun Ahn, Inbo Han, Dong Keun Han Biomaterials Research.2026;[Epub] CrossRef
Pharmacological METTL3 inhibition attenuates HIV-1 latency reversal in CD4
+
T cells
Tarun Mishra, Avary Edwards, Li Wu, Zhaohui Qian Antimicrobial Agents and Chemotherapy.2026;[Epub] CrossRef
Machine learning-assisted prediction of PANoptosis-related molecular targets and precise screening of neuroprotective drugs for spinal cord injury Dongmei Wang, Rui Wang, Huangmei Liao, Feiyang Lu, Zepeng Guo, Ruijun Xu, Aini Chen, Zhen Niu, Yusen Ou, Ge Li Experimental Neurology.2026; 404: 115884. CrossRef
Roles of METTL3 and NLRP3 in pyroptosis and prospects in SCIRI Xiaoqing Guan, Fengyi Zhang, Ning Zhang, Guangchun Li, Fei Yin Frontiers in Immunology.2025;[Epub] CrossRef
Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury Lahanya Guha, Divya Goyal, Nidhi Singh, Mamidi Teena, Inbo Han, Hemant Kumar Molecular Neurobiology.2025; 62(10): 13763. CrossRef
m6A-RNA epitranscriptomes regulate splicing and neuronal development in the Pacific oyster Crassostrea gigas Natacha Clairet, Hélène Auger, Roberto-Carlos Arredondo-Espinoza, Hugo Koechlin, Benoît Bernay, Lukas Manoury, Didier Goux, Guillaume Rivière Genomics.2025; 117(6): 111142. CrossRef
METTL3 improves spinal cord injury-associated locomotor function via SIRT1 m6A modification and regulation of neuronal ferroptosis Ying Chen, Kaibin Zeng, Gongzhou Chen, Ruiqi Yang, Lian Wu, Shaolin Li, Bin Hu Neurological Research.2025; : 1. CrossRef
Potential Pharmacologic Treatments in Spinal Cord Injury: A Narrative Review Kyeong Deuk An, Chan Yang Noh, Junsoo Jang, Woon Tak Yuh, Il Choi Korean Journal of Neurotrauma.2025; 21(4): 237. CrossRef
Objective The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.
Methods By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.
Results The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.
Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
Citations
Citations to this article as recorded by
Niche-targeted paracrine signaling from OMSCs restores the regenerative microenvironment after SCI Zhe Wang, Ruijie Feng, Wanjing Rong, Xu Shi, Qingtong Yu, Wenwen Deng, Xia Cao, Qilong Wang, Jollibekov Berdiyar, Mohammad Had Eskandari, Jiangnan Yu, Ximing Xu Biofabrication.2026; 18(1): 015020. CrossRef
Cellular iron flux measurement by micromagnetic resonance relaxometry as a critical quality attribute of mesenchymal stromal cells Yanmeng Yang, Meiqi Kang, Mengli Chen, Liang Cui, Zheng Yang, Jongyoon Han Stem Cells Translational Medicine.2026;[Epub] CrossRef
Intercellular propagation of ferroptosis Jian Yang, Ying Gao Advances in Redox Research.2026; 18: 100153. CrossRef
Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration Yuzhu Xu, Zhanyang Qian, Mingliang Ji, Jun Lu Apoptosis.2026;[Epub] CrossRef
Multimodal electroconductive PLGA-based scaffold orchestrates neuroprotection and regeneration following severe spinal cord injury So-Yeon Park, Gyubin Kim, Yanting Liu, Ji-Won Jung, Jeoung Eun Lee, Jun-Kyu Lee, Dong-Hee Kim, Juwon Youn, Seung-Woon Baek, Dong Ryul Lee, Dong-Youn Hwang, Tae-Keun Ahn, Da-Seul Kim, Inbo Han, Dong Keun Han Journal of Nanobiotechnology.2026;[Epub] CrossRef
HIF-1α at the intersection of hypoxia, ferroptosis-associated stress, and cell death crosstalk in osteomyelitis Jinglin Li, Fuyin Yang, Xuan Deng, Yang Yu, Xianpeng Huang, Xuxu Yang, Lidan Yang, Tao Zhang, Huazhang Xiong Frontiers in Cell and Developmental Biology.2026;[Epub] CrossRef
Targeting Nrf2-mediated regulation of ferroptosis: A novel therapeutic approach for orthopedic diseases Lei Huang, Xianghong Wang, Xianxu Zhang, Shicheng Li, Yuji Zhang, Yong Sun, Changlin Zhou, Bin Qian, Zhiqiang Luo Genes & Diseases.2026; : 102058. CrossRef
Umbilical cord mesenchymal stem cells and their extracellular vesicles attenuate cryopreservation-induced ovarian injury via the suppression of ferroptosis in an in vitro culture system Wenjuan Xu, Xiang Yao, Chen Chen, Mengyao Wang, Yaxin Chen, Dan Liang, Qun Gao, Xianwen Wang, Ping Zhou, Jianye Wang Materials Today Bio.2026; 37: 102965. CrossRef
NanoScript-Enabled Nonviral Transient Repression of Phosphatase and Tensin Homolog for Axonal Regeneration and Central Nervous System Injury Repair Brandon Conklin, Yanting Liu, Sarah Nevins, Byeong-Gwan Song, Sy-Tsong Dean Chueng, Qiu Xiaowen, Sungyun Kim, Heyin Cheung, Seong Bae An, JongMin Lee, Bong Geun Chung, Wise Young, Dongming Sun, Hiroshi Sugiyama, Inbo Han, Ki-Bum Lee ACS Nano.2026; 20(8): 6582. CrossRef
Activation of Nrf2 with natural flavonoids and mesenchymal stromal/stem cells: mechanisms and therapeutic potential for inflammatory diseases Fengqing Shang, Yanling Qu, Zhe Wang, Lingjuan Dong, Afeng Li, Dan Zhang, Sha Gong, Yanni Gao, Qinhua Bai, Leiguo Ming, Longquan Shao Stem Cell Research & Therapy.2026;[Epub] CrossRef
Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han International Journal of Molecular Sciences.2026; 27(4): 2079. CrossRef
3D bioprinted multifunctional GelMA/TMP scaffold integrated with neural stem cell-derived extracellular vesicles and neural progenitor cells for spinal cord injury repair Yanting Liu, Gyubin Kim, Jun Yong Kim, Jeong Min Park, Duck Hyun Song, Jun-Kyu Lee, So-Yeon Park, Inbo Han, Dong Keun Han Journal of Tissue Engineering.2026;[Epub] CrossRef
Liproxstatin-1 improves functional recovery after acute spinal cord injury by inhibiting ferroptosis-induced inflammation Pan Lei, Jiangtao Yu, Haoli Ma, Fan Yao, Xiaoqing Jin Molecular and Cellular Neuroscience.2026; 137: 104078. CrossRef
Single-cell RNA sequencing analysis of lymphocyte responses to combined stem cell therapies in a rat model of spinal cord injury Yan He, Qi-Qin Dan, Peng Zhang New Cell.2026;[Epub] CrossRef
Oxidative Stress‐Related Programmed Cell Death in Male Infertility: Focussing on Ferroptosis Nafiseh Sanei‐Ataabadi, Fatemeh Aboutalebi, Kianoush Dormiani, Mohammad Hossein Nasr‐Esfahani Journal of Cellular and Molecular Medicine.2026;[Epub] CrossRef
Exosomes in organ transplantation: roles in immunomodulation, ferroptosis and mitophagy Yunuo Jiang, Peiran Xu, Tianyun Gao, Chong Wang, Meng Fan, Zhantong Tang, Koulong Zheng, Pengyu Liu Frontiers in Immunology.2026;[Epub] CrossRef
Research status and prospective directions of ferroptosis in the pathogenesis of vascular calcification Jingjing Ke, Hualong Zang, Dan Peng, Ping Wang Tissue and Cell.2026; 103: 103672. CrossRef
Mesenchymal stem cell-derived small extracellular vesicles in spinal cord injury: From molecular repair mechanisms to standardized translational development Arwa Omar Al Khatib, Ulugbek Akhmedov, Djaloliddin Mansurov, Rhab Mazy Jbar, K.V. Jamuna, Laxmidhar Maharana, Neeraj Bainsal, Divya Singhal Journal of Neuroscience Methods.2026; 435: 110861. CrossRef
VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis Juan Yang, Xiao Lu, Jing-Lan Hao, Lan Li, Yong-Tong Ruan, Xue-Ni An, Qi-Lai Huang, Xiao-Ming Dong, Ping Gao Nature Communications.2025;[Epub] CrossRef
Pre-treated mesenchymal stem cell-derived exosomes: A new perspective for accelerating spinal cord injury repair Zhiqiang Liao, Junjian Zeng, Aiqing Lin, Yu Zou, Zhidong Zhou European Journal of Pharmacology.2025; 992: 177349. CrossRef
Ferroptosis in neurodegenerative diseases: mechanisms and therapeutic potential of stem cell derivatives Ting Zhang, Yusu Zhang, Jinpeng Xie, Dandan Lu, Lihong Wang, Shuaifei Zhao, Jing Zhou, Yang Cheng, Ting Kou, Jue Wang, Ying Chen, Lei Xu, Xiangyu Hu, Yuxiu Ying, Jun Wang, Xiaoshuang Xin, Xu Xu, Siyun Lei, Chenyu Qiu, Jinhua Wu, Qiqi Lyu, Tong Cao Frontiers in Cell and Developmental Biology.2025;[Epub] CrossRef
Mesenchymal stem cell-derived exosomes as a potential therapeutic strategy for ferroptosis Mohammed Zayed, Enas Elwakeel, Prehan Ezzat, Byung-Hoon Jeong Stem Cell Research & Therapy.2025;[Epub] CrossRef
Mechanistic insights into Nrf2-driven pathogenesis and therapeutic targeting in spinal cord injury Tao Xie, Jiyu Xu, Xinyu Liu, Yaquan Yu, Yang Lu, Tao Wang, Feng Gao, Hui Yuan Frontiers in Immunology.2025;[Epub] CrossRef
Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury Lahanya Guha, Divya Goyal, Nidhi Singh, Mamidi Teena, Inbo Han, Hemant Kumar Molecular Neurobiology.2025; 62(10): 13763. CrossRef
IMRC-exo alleviates limb injury by inhibiting ferroptosis in a rabbit model of deinagkistrodon acutus snakebite envenomation Linjie Lai, Wang Du, Haohao Wu, Wanjuan Liu, Ke lv, Peixin Shangguan, Lutao Xie, Jiefeng Xu, Pin Lan Scientific Reports.2025;[Epub] CrossRef
Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies Xia Han, Rongdong Liao, Xiang Li, Cantong Zhang, Shaochuan Huo, Lei Qin, Yi Xiong, Tailin He, Guozhi Xiao, Tianfeng Zhang Signal Transduction and Targeted Therapy.2025;[Epub] CrossRef
Extracellular Vesicles: A New Dimension in Nerve Injury Repair Miaomei Yu, Yang Yu, Jiayi Zhou, Jiang Wei, Liuchang Song, Jun Zhang, Lu Zheng, Fei Ding Engineering.2025;[Epub] CrossRef
LARP4B inhibits ferroptosis and accelerates the progression of pancreatic cancer by activating WNK1-induced NRF2/GCH1/BH4 pathway Jiehao Tu, Lun Zhang Integrative Biology.2025;[Epub] CrossRef
Ferroptosis in Spinal Cord Injury: Research Progress and Novel Insights Shizhe Li, Shutao Gao, Yukun Hu, Guangxu Sun, Jingsheng Feng, Weibin Sheng Journal of Cellular Biochemistry.2025;[Epub] CrossRef
Advanced Biomaterial Delivery of Hypoxia‐Conditioned Extracellular Vesicles (EVs) as a Therapeutic Platform for Traumatic Brain Injury Joshua B. Stein, Songzi Zhang, Eun Ji Roh, Jeffrey Luo, Meizi Chen, Hyunjun Jang, Li Ling Goldston, Brandon Conklin, Inbo Han, Ki‐Bum Lee Advanced Science.2025;[Epub] CrossRef
Human amniotic mesenchymal stem cell-derived exosome inhibits ferroptosis through the suppression of JNK/MAPK-mediated EGR1 expression in spontaneous intracerebral hemorrhage Yiheng Wang, Liangfu Zhou, Kan Xu Brain Research Bulletin.2025; 231: 111553. CrossRef
Disruptions in nitric oxide homeostasis, lipid peroxidation-derived oxidative stress, and antioxidant defense mechanisms in spinal cord injury: elucidating biomolecular correlates of disease severity Mohd Mursal, Irfan Hasan, Babita Tiwari, Rajesh K. Srivastava, Ganesh Yadav, Ghizal Fatima Molecular Biology Reports.2025;[Epub] CrossRef
Potential Pharmacologic Treatments in Spinal Cord Injury: A Narrative Review Kyeong Deuk An, Chan Yang Noh, Junsoo Jang, Woon Tak Yuh, Il Choi Korean Journal of Neurotrauma.2025; 21(4): 237. CrossRef
Mesenchymal stem cell-derived extracellular vesicles for disease therapy by regulating ferroptosis: focus on diabetes mellitus and diabetic complications Jiayuan Wu, Zixuan Zhou, Hui Qian Stem Cell Research & Therapy.2025;[Epub] CrossRef
Exosome-mediated repair of spinal cord injury: cellular sources, mechanisms of action, and combined therapeutic strategies Zaihong Cha, Yu Li, Jianeng Pu, Yuansheng Zhang, Qixiong Lu, Wei Huang, Tao Li, Xiaoyang Lu Frontiers in Neurology.2025;[Epub] CrossRef
Multifunctional nanoplatforms for optic nerve regeneration integrating anti-inflammatory, epigenetic, and ionic mechanisms with emerging artificial intelligence technologies Tian Wang, Shan Huang, Jiayi Wu, Wenzhi Shi Cell Biology and Toxicology.2025;[Epub] CrossRef
Regulated cell death in cancer: Mechanisms, crosstalk, and opportunities for therapy Yimei Meng, Qun Chen, Zhijun Zhou, Min Li Cancer Letters.2025; 635: 218077. CrossRef
The role of ferroptosis in the pathogenesis of pulmonary hypertension and its therapeutic potential Yaqian Bai, Yuanhang Jiang, Yibo Zhou, Yuxi Xia, Fanrong Zhao, Yujing Chen, Tiantian Zhu European Journal of Pharmacology.2025; 1008: 178316. CrossRef
Effects and mechanisms of MSCs and MSC-derived exosomes in regulating ferroptosis Zhiliang Guo, Zhuojian Qu, Yubing Zhang, Donghua Xu, Lijuan Chu, Min Cheng Journal of Physiology and Biochemistry.2025; 81(4): 1001. CrossRef
Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction Sung Jun Hong, Minsung Bock, Songzi Zhang, Seong Bae An, Inbo Han International Journal of Molecular Sciences.2024; 25(15): 8540. CrossRef
The Potential of Mesenchymal Stem Cell-Derived Exosomes in Cardiac Repair Dipan Kundu, Song Yi Shin, William M. Chilian, Feng Dong International Journal of Molecular Sciences.2024; 25(24): 13494. CrossRef
Advancements in Antioxidant-Based Therapeutics for Spinal Cord Injury: A Critical Review of Strategies and Combination Approaches Yang-Jin Shen, Yin-Cheng Huang, Yi-Chuan Cheng Antioxidants.2024; 14(1): 17. CrossRef
Objective Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery.
Methods We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3–12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum).
Results The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004–1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67.
Conclusion Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.
Citations
Citations to this article as recorded by
A novel Minimally-Invasive technique for Non-Traumatic postoperative adhesive Syringomyelia Can Zhang, Chenghua Yuan, Jiachen Wang, Hao Wu, Zan Chen, Fengzeng Jian, Jian Guan European Spine Journal.2026; 35(4): 2095. CrossRef
Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic Advances Trung Nhan Vo, Hae Eun Shin, Yeji Kim, Inbo Han International Journal of Molecular Sciences.2026; 27(4): 2079. CrossRef
Objective Herein, we investigated whether mesenchymal stem cells (MSCs) transplantation combined with electroacupuncture (EA) treatment could decrease the proportion of proinflammatory microglia/macrophages and neurotoxic A1 reactive astrocytes and inhibit glial scar formation to enhance axonal regeneration after spinal cord injury (SCI).
Methods Adult rats were divided into 5 groups after complete transection of the spinal cord at the T10 level: a control group, a nonacupoint EA (NA-EA) group, an EA group, an MSC group, and an MSCs+EA group. Immunofluorescence labeling, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blots were performed.
Results The results showed that MSCs+EA treatment reduced the proportion of proinflammatory M1 subtype microglia/macrophages, but increased the differentiation of anti-inflammatory M2 phenotype cells, thereby suppressing the mRNA and protein expression of proinflammatory cytokines (tumor necrosis factor-α and IL-1β) and increasing the expression of an anti-inflammatory cytokine (interleukin [IL]-10) on days 7 and 14 after SCI. The changes in expression correlated with the attenuated neurotoxic A1 reactive astrocytes and glial scar, which in turn facilitated the axonal regeneration of the injured spinal cord. In vitro, the proinflammatory cytokines increased the level of proliferation of astrocytes and increased the expression levels of C3, glial fibrillary acidic protein, and chondroitin sulfate proteoglycan. These effects were blocked by administering inhibitors of ErbB1 and signal transducer and activator of transcription 3 (STAT3) (AG1478 and AG490) and IL-10.
Conclusion These findings showed that MSCs+EA treatment synergistically regulated the microglia/macrophage subpopulation to reduce inflammation, the formation of neurotoxic A1 astrocytes, and glial scars. This was achieved by downregulating the ErbB1-STAT3 signal pathway, thereby providing a favorable microenvironment conducive to axonal regeneration after SCI.
Citations
Citations to this article as recorded by
The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies Rui Wang, Zhen Niu, Runze Tian, Aini Chen, Huangmei Liao, Rui Kuang, Ying Feng, Guangyu Chin, Jiesheng Xie, Ping Zhu, Chi Teng Vong, Ge Li Neural Regeneration Research.2026; 21(6): 2110. CrossRef
Mesenchymal stem cells transplantation as a replacement stem cell for the treatment of neuropathic pain Wen-Jun Zhang, Xin Zhang, Ji-Peng Liu, Yong-Sheng Xu, Jun-Xiang Liao, Bing Zou, Liu-Xiang Fu International Journal of Surgery.2026; 112(3): 7906. CrossRef
STAT3 Signaling in Spinal Cord Injury: Neurochemical Mechanisms Linking Neuroinflammation, Mitochondrial Stress, and Glial Remodeling Da Wei, Jinsan Yang, Xiao He, Kang Li, Chaoliang Lv, Kai Gao Neurochemical Research.2026;[Epub] CrossRef
Electroacupuncture-modulated DHCR24 facilitates spinal cord injury recovery by attenuating apoptosis and neuroinflammation via the Wnt signaling pathway Chunlei Li, Yuan Li, Tongyan Liu, Yue Zong, Lingyun Zhou Metabolic Brain Disease.2026;[Epub] CrossRef
Glial cell: Role of the pain modulation in acupuncture analgesia Mi YUAN, Lan YUAN, Wei CHEN, Yang-shuai SU, Meng-yan FAN, Xiang-hong JING, Wei HE, Xiao-yu WANG World Journal of Acupuncture - Moxibustion.2025; 35(2): 103. CrossRef
Biomaterials and cell-based therapy post spinal cord injury Sara Haratizadeh, Haitao Liu, Hengde Li, Mohsen Adeli, Angelo H. All Journal of Translational Medicine.2025;[Epub] CrossRef
Integrated single-cell and bulk RNA sequencing reveals the mechanisms of electroacupuncture in suppressing ferroptosis after spinal cord injury Jieqi Zhang, Yi Huang, Xihan Ying, Ruoqi Wang, Kai Zhang, Lei Wu, Dexiong Han, Ruijie Ma, Kelin He Clinical Traditional Medicine and Pharmacology.2025; 6(3): 200230. CrossRef
Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction Sung Jun Hong, Minsung Bock, Songzi Zhang, Seong Bae An, Inbo Han International Journal of Molecular Sciences.2024; 25(15): 8540. CrossRef
Objective Electroacupuncture (EA) has a definite effect on the treatment of spinal cord injuries (SCIs), but its underlying molecular mechanism remains unclear. Meanwhile, MiR106b-5p is an autophagy- and apoptosis-related microribonucleic acid, but whether it regulates the progression of autophagy and apoptosis in SCIs is yet undetermined. As such, this study aimed to elucidate the involvement of miR-106b-5p in the EA treatment of an SCI.
Methods The miR-106b-5p level was detected by quantitative real-time polymerase chain reaction. In vitro, SH-SY5Y cells were transfected with miR-106b-5p mimics or inhibitors to regulate the miR-106b-5p expression, while in vivo, SCI rats were treated with EA for 7 days at the bilateral Zusanli (ST36) and Jiaji (EX-B2) acupoints. The motor function was evaluated using the Basso-Beattie-Bresnahan (BBB) criteria. Further, autophagic vacuoles, pathological damage, and neuronal cell morphology were observed by transmission electron microscopy, as well as by hematoxylin and eosin and Nissl staining, respectively.
Results The miR-106b-5p level, which can interact directly with Beclin-1 by influencing its expression, as well as the expressions of P62, Caspase-3, and Bax, was upregulated after an SCI, but it decreased after EA. Moreover, the ratio of LC3-II to LC3-I was upregulated after EA. EA can enhance autophagy, reduce neuronal apoptosis, and minimize motor dysfunction and histopathological deficits after an SCI. More importantly, however, all the above effects induced by EA can be reversed after an injection of miR-106-5p agomir to produce an overexpression of miR-106b-5p.
Conclusion EA treatment could downregulate miR-106b-5p to alleviate SCI-mediated injuries by promoting autophagy and inhibiting apoptosis.
Citations
Citations to this article as recorded by
Electroacupuncture enhances the effects of escitalopram oxalate on glucocorticoid-inducible genes, inflammation and neurotrophin in depressed patients Xinjing Yang, Bingcong Zhao, Jing Li, Chuan Shi, Xingzhou Gao, Yangpeng Wang, Huili Jiang, Shixing Feng, Tuya Bao, Zhangjin Zhang Journal of Traditional and Complementary Medicine.2026; 16(2): 143. CrossRef
Acupuncture alleviates inflammatory pain by regulating microglial polarization through α7nAchR-mediated autophagy Guo-qi Dong, Hui Gao, Yi-jun Sun, Qiu-hong Yang, Yong Yao, Hua-yuan Yang Journal of Integrative Medicine.2026; 24(3): 429. CrossRef
The Mechanism of Acupuncture Regulating Autophagy: Progress and Prospect Jing He, Min He, Mengmeng Sun, Hongxiu Chen, Zhiqiang Dou, Ru Nie, Jun Zhou, Qingqing Tang, Cong Che, Jie Liu, Tie Li Biomolecules.2025; 15(2): 263. CrossRef
Objective Spinal cord injury (SCI) is a severe type of neurological trauma. N6-methyladenosine (m6A) modification is one of the most common internal modifications of RNA. The role of METTL3, the predominant methylation enzyme of m6A modification, in SCI remains unclear. This study aimed to investigate the role of methyltransferase METTL3 in SCI.
Methods After establishing the oxygen-glucose deprivation (OGD) model of PC12 cells and rat spinal cord hemisection model, we found that the expression of METTL3 and the overall m6A modification level were significantly increased in neurons. The m6A modification was identified on B-cell lymphoma 2 (Bcl-2) messenger RNA (mRNA) by bioinformatics analysis, and m6A-RNA immunoprecipitation and RNA immunoprecipitation. In addition, METTL3 was blocked by the specific inhibitor STM2457 and gene knockdown, and then apoptosis levels were measured.
Results In different models, we found that the expression of METTL3 and the overall m6A modification level were significantly increased in neurons. After inducing OGD, inhibition of METTL3 activity or expression increased the mRNA and protein levels of Bcl-2, inhibited neuronal apoptosis, and improved neuronal viability in the spinal cord.
Conclusion Inhibition of METTL3 activity or expression can inhibit the apoptosis of spinal cord neurons after SCI through the m6A/Bcl-2 signaling pathway.
Citations
Citations to this article as recorded by
Interaction between N6-methyladenosine (m6A) modification and toxicant-related neurodegeneration: From neural development to pathophysiology Zhou She, Peng Huang, Senlin Luo, Lu Zhang, Hong Peng, Yufen Tang, Yuqiong Chen, Jinwen Luo, Wangxin Duan, Lingjuan Liu, Liqun Liu Genes & Diseases.2026; 13(5): 101984. CrossRef
The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies Rui Wang, Zhen Niu, Runze Tian, Aini Chen, Huangmei Liao, Rui Kuang, Ying Feng, Guangyu Chin, Jiesheng Xie, Ping Zhu, Chi Teng Vong, Ge Li Neural Regeneration Research.2026; 21(6): 2110. CrossRef
Methyltransferase-like protein 16 suppresses spinal cord injury by regulating microglia polarization via N6-methyladenosine-modified downregulation of MCEMP1 Lei Zhang, Haijun Chang, Guangming Jiang, Chao Zhu, Shan Zhou, Yanling Wang, Hui Chang Journal of Neuropathology & Experimental Neurology.2026; 85(5): 487. CrossRef
m6A epitranscriptomic remodeling links redox stress to mitochondrial quality control and programmed cell death in sepsis-induced myocardial dysfunction Meilian Chen, Binlan Fu, Qiaomin Wu Redox Biology.2026; 93: 104178. CrossRef
Actl6a regulates autophagy via Sox2-dependent Atg5 and Atg7 expression to inhibit apoptosis in spinal cord injury Jian Hao, Yubiao Yang, Li Xie, Zhenhan Li, Boyuan Ma, Bitao Wang, Jinyu Chen, Zhi Zeng, Xianhu Zhou Journal of Advanced Research.2025; 77: 281. CrossRef
Molecular mechanism of METTL3 regulating hippocampal neuronal injury induced by sepsis-associated encephalopathy Qian Zhang, Yan Huo, Runying Zhu, Xujie Zhang, Lingwei Zeng, Zhenjie Hu Archives of Physiology and Biochemistry.2025; 131(4): 582. CrossRef
Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury Lahanya Guha, Divya Goyal, Nidhi Singh, Mamidi Teena, Inbo Han, Hemant Kumar Molecular Neurobiology.2025; 62(10): 13763. CrossRef
m6A mRNA Methylation in Hematopoiesis: The Importance of Writing, Erasing, and Reading Antonia-Gerasimina Vasilopoulou, Eleni Kalafati, Ekati Drakopoulou, Nicholas P. Anagnou Cells.2025; 14(17): 1388. CrossRef
METTL3 Promotes Mitochondrial Dysfunction and Neuronal Ferroptosis in Cerebral Ischemia and Reperfusion Injury through YTHDC1/SLC7A11 Modification
Boyu Chen, Ruoyu Deng, Yifei Chen, Sanxi Lei, Wei Xia Critical Reviews in Eukaryotic Gene Expression.2025; 35(6): 59. CrossRef
Hydrogen sulfide protects against hippocampal neuronal apoptosis in aged rats with postoperative cognitive dysfunction by promoting m6A methylation Bo Wang, YongPan Wen, Yonghong Tang, Min Li Neuroscience Letters.2025; 868: 138405. CrossRef
N6-methyladenosine reader YTHDF1 mediates neuronal apoptosis induced by aluminum via m6A/Bcl-2 manner Jing Song, Xiaohui Ding, Mujia Li, Yulu Xin, Yang Lu, Xiaojuan Yang, Xiaoting Lu Ecotoxicology and Environmental Safety.2025; 306: 119270. CrossRef
METTL3 improves spinal cord injury-associated locomotor function via SIRT1 m6A modification and regulation of neuronal ferroptosis Ying Chen, Kaibin Zeng, Gongzhou Chen, Ruiqi Yang, Lian Wu, Shaolin Li, Bin Hu Neurological Research.2025; : 1. CrossRef
Knockout of METTL3 promotes neural functional recovery after spinal cord injury in mice via the USP4/YTHDF2 axis Yanbo Yu, Zhisheng Wu, Ziqiang Yu, Daying Zhang Molecular & Cellular Toxicology.2024; 20(4): 861. CrossRef
Mechanism of Fat Mass and Obesity‐Related Gene‐Mediated Heme Oxygenase‐1 m6A Modification in the Recovery of Neurological Function in Mice with Spinal Cord Injury Jinghui Xu, Zhenxiao Ren, Tianzuo Niu, Siyuan Li Orthopaedic Surgery.2024; 16(5): 1175. CrossRef
METTL3 promotes the osteogenic differentiation of periosteum-derived MSCs via regulation of the HOXD8/ITGA5 axis in congenital pseudarthrosis Weihua Ye, Zheng Liu, Yaoxi Liu, Han Xiao, Qian Tan, An Yan, Guanghui Zhu Regenerative Therapy.2024; 26: 42. CrossRef
Methyltransferase-Like 3–Driven N6-Methyladenosine Modification of Recombination Signal Binding Protein for Immunoglobulin Kappa J Region Promotes Vascular Remodeling in Pulmonary Hypertension Qiang Du, Chun Zhang, Tianyu Qu, Xiao Zhou, Yingying Liu, Zhixuan Chen, Ziling Shen, Pingsheng Chen, Ruifeng Zhang The American Journal of Pathology.2024; 194(12): 2252. CrossRef
STM2457 Inhibits METTL3-Mediated m6A Modification of miR-30c to Alleviate Spinal Cord Injury by Inducing the ATG5-Mediated Autophagy Gang Chen, Zhitao Shangguan, Xiaoqing Ye, Zhi Chen, Jiandong Li, Wenge Liu Neurospine.2024; 21(3): 925. CrossRef
METTL3 inhibits microglial pyroptosis in neonatal hypoxia-ischemia encephalopathy by regulating GPR39 expression in an m6A-HuR-dependent manner Xili Jiang, Wei Zhang, Shucai Xie Neuroscience.2024; 563: 175. CrossRef
From the Editor-in-Chief: Featured Articles in the June 2023 Issue Inbo Han Neurospine.2023; 20(2): 413. CrossRef
Formononetin ameliorates the LPS-induced inflammatory response and apoptosis of neuronal cells via NF-κB/NLRP3 signaling pathway Zhijing Zhou, Peng Zhang Functional & Integrative Genomics.2023;[Epub] CrossRef
Molecular and cellular mechanisms of neuronal apoptosis following spinal cord injury Chang-Yan Hu New Cell.2023;[Epub] CrossRef
After spinal cord injury (SCI), endogenous neural stem cells are activated and migrate to the injury site where they differentiate into astrocytes, but they rarely differentiate into neurons. It is difficult for brain-derived information to be transmitted through the injury site after SCI because of the lack of neurons that can relay neural information through the injury site, and the functional recovery of adult mammals is difficult to achieve. The development of bioactive materials, tissue engineering, stem cell therapy, and physiotherapy has provided new strategies for the treatment of SCI and shown broad application prospects, such as promoting endogenous neurogenesis after SCI. In this review, we focus on novel approaches including tissue engineering, stem cell technology, and physiotherapy to promote endogenous neurogenesis and their therapeutic effects on SCI. Moreover, we explore the mechanisms and challenges of endogenous neurogenesis for the repair of SCI.
Construction of a rodent neural network-skeletal muscle assembloid that simulate the postnatal development of spinal cord motor neuronal network Haiyang Yu, Shangbin Yang, Yuanfeng Chen, Chuangran Wu, Jing Xu, Yue Yang, Rongjie Wu, Yinan Guo, Zhen Chen, Ying Ding, Xiang Zeng, Ge Li, Yuanhuan Ma, Qiujian Zheng, Yuanshan Zeng, Biqin Lai Scientific Reports.2025;[Epub] CrossRef
The Role of Dopamine in Chronic Pain: Neuroinflammation and Neurogenesis A. Vetlugina, N. O. Fokeeva, A. A. Kochneva, A. V. Kalueff, P. E. Musienko, E. V. Gerasimova Journal of Evolutionary Biochemistry and Physiology.2025; 61(2): 514. CrossRef
Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury Lahanya Guha, Divya Goyal, Nidhi Singh, Mamidi Teena, Inbo Han, Hemant Kumar Molecular Neurobiology.2025; 62(10): 13763. CrossRef
Enhancing Functional Recovery After Spinal Cord Injury Through Neuroplasticity: A Comprehensive Review Yuan-Yuan Wu, Yi-Meng Gao, Ting Feng, Jia-Sheng Rao, Can Zhao International Journal of Molecular Sciences.2025; 26(14): 6596. CrossRef
Spinal cord transection repair occurs when Nestin+ cells differentiate into neurons within a taxol‐collagen‐enhanced microenvironment in mice Caixia Fan, He Jiang, Junyan Yan, Lifang Jin, Guoquan Fu, Weiwei Xue, Lulu Zhang Neuroprotection.2025; 3(4): 358. CrossRef
The Glial Scar: To Penetrate or Not for Motor Pathway Restoration? Tetsuji Sekiya, Matthew C. Holley Cell Transplantation.2025;[Epub] CrossRef
Innovative Strategies in 3D Bioprinting for Spinal Cord Injury Repair Daniel Youngsuk Kim, Yanting Liu, Gyubin Kim, Seong Bae An, Inbo Han International Journal of Molecular Sciences.2024; 25(17): 9592. CrossRef
Unravelling the Road to Recovery: Mechanisms of Wnt Signalling in Spinal Cord Injury Suchita Ganesan, Arun Dharmarajan, G Sudhir, Lakshmi R. Perumalsamy Molecular Neurobiology.2024; 61(10): 7661. CrossRef
A core scientific problem in the treatment of central nervous system diseases: newborn neurons Peng Hao, Zhaoyang Yang, Kwok-Fai So, Xiaoguang Li Neural Regeneration Research.2024; 19(12): 2588. CrossRef
Improved Recovery of Complete Spinal Cord Transection by a Plasma-Modified Fibrillar Scaffold Diana Osorio-Londoño, Yessica Heras-Romero, Luis B. Tovar-y-Romo, Roberto Olayo-González, Axayácatl Morales-Guadarrama Polymers.2024; 16(8): 1133. CrossRef
Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction Sung Jun Hong, Minsung Bock, Songzi Zhang, Seong Bae An, Inbo Han International Journal of Molecular Sciences.2024; 25(15): 8540. CrossRef
Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury Lahanya Guha, Nidhi Singh, Hemant Kumar Neurospine.2023; 20(2): 430. CrossRef
The Role of Exercise in the Alleviation of Neuropathic Pain Following Traumatic Spinal Cord Injuries: A Systematic Review and Meta-analysis Amirmohammad Toloui, Hamzah Adel Ramawad, Pantea Gharin, Alexander R. Vaccaro, Hamed Zarei, Mostafa Hosseini, Mahmoud Yousefifard, Vafa Rahimi-Movaghar Neurospine.2023; 20(3): 1073. CrossRef
Cell death is a systematic/nonsystematic process of cessation of normal morphology and functional properties of the cell to replace and recycle old cells with new also promoting inflammation in some cases. It is a complicated process comprising multiple pathways. Some are well-explored, and others have just begun to be. The research on appropriate control of cell death pathways after acute and chronic damage of neuronal cells is being widely researched today due to the lack of regeneration and recovering potential of a neuronal cell after sustaining damage and the inability to control the direction of neuronal growth. In the progression and onset of various neurological diseases, impairments in programmed cell death signaling processes, like necroptosis, apoptosis, ferroptosis, pyroptosis, and pathways directly or indirectly linked, like autophagy as in nonprogrammed necrosis, are observed. Spinal cord injury (SCI) involves the temporary or permanent disruption of motor activities due to the death of a neuronal and glial cell in the spinal cord accompanied by axonal degeneration. Recent years have seen a significant increase in research on the intricate biochemical interactions that occur after a SCI. Different cell death pathways may significantly impact the subsequent damage processes that lead to the eventual neurological deficiency after an injury to the spinal cord. A better knowledge of the molecular basis of the involved cell death pathways might help enhance neuronal and glial survival and neurological deficits, promoting a curative path for SCI.
Citations
Citations to this article as recorded by
Nano-shields: Exploring the role of antioxidant mimicking nanoparticles as regenerative therapy in spinal cord injury Nidhi Singh, Lahanya Guha, Zarna Pathak, Hemant Kumar Biomaterials Advances.2026; 178: 214484. CrossRef
Integrated Bioinformatic Analysis and Experimental Validation for Crosstalk Among Various Forms of Cell Death in Spinal Cord Injury Kuileung Tong, Jianfeng Li, Shan Li, Shiming Li, Guoliang Chen, Shaoyu Liu, Yuhang Li, Ningning Chen, Bin Liu Molecular Neurobiology.2026;[Epub] CrossRef
Targeting microglial PANoptosis through AMPK activation: Metformin as a promising therapy for spinal cord injury Song Liu, Mi Zhou, Cong Xing, Zhenxing Guo, Qi Zhang, Hongpeng Ma, Hao Zhong, Hongjiang Yang, Guangzhi Ning Journal of Pharmaceutical Analysis.2026; 16(5): 101556. CrossRef
The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies Rui Wang, Zhen Niu, Runze Tian, Aini Chen, Huangmei Liao, Rui Kuang, Ying Feng, Guangyu Chin, Jiesheng Xie, Ping Zhu, Chi Teng Vong, Ge Li Neural Regeneration Research.2026; 21(6): 2110. CrossRef
PANoptosis: a new perspective for targeting programmed cell death after spinal cord injury Qiheng Qian, Lei Shi, Jiding Xie, Xinyu Zhao, Xiangqi Meng Frontiers in Immunology.2026;[Epub] CrossRef
Neuroprotection or Neurotoxicity? Insights from preclinical and clinical studies of methotrexate in spinal cord injury Amir Azimi, Mohammadhossein Vazirizadeh-Mahabadi, Mobina Yarahmadi, Arash Sarveazad, Mahmoud Yousefifard Surgical Neurology International.2026; 17: 100. CrossRef
c-Jun in neurodegeneration: A key transcriptional regulator with therapeutic implications Faiz Ali Khan, Hizbullah Khan, Usman Ayub Awan, Mammat Nurahmat, Mohammadtursun Nabijan, Muhammadjan Abduwaki, Jingcheng Dong Molecular Therapy Nucleic Acids.2026; 37(2): 102874. CrossRef
Exosome-derived ncRNAs and proteins: inflammation regulatory mechanisms and biomarker potential in spinal cord injury Yongliang Wang, Jian Zhang, Jinsheng Liu, Yuefeng Li, Xinyu Zhao, Zhixin Yang Frontiers in Molecular Biosciences.2026;[Epub] CrossRef
Exosomes as regenerative therapeutics for spinal cord injury: mechanisms and clinical prospects Yingbo Xiao, Tao Cui, Ying Zhou, Qichao Su, Duan Yi Frontiers in Medicine.2026;[Epub] CrossRef
Chronic Loud Noise—Biochemical and Ultrastructural Alterations in Auditory and Limbic Regions of the Rat Brain Nino Pochkhidze, Lela Chitadze, Lia Tsverava, Giorgi Lobzhanidze, Nadezhda Japaridze, Fuad Rzayev, Eldar Gasimov, Mzia G. Zhvania, Revaz Solomonia, Poorani Gurumallesh Prabu BioMed Research International.2026;[Epub] CrossRef
Calretinin and Parvalbumin Trapping of TDP43 and XRCC1 Instructs Neocortical Interneuron Death in Neonatal Hypoxic-Ischemic Encephalopathy Lee J. Martin, Rebecca N. Ichord, Caitlin E. O’Brien, Sophie Yohannan, Danay Fernandez, Annalise Garrido, Naya Amauri, Dongseok Park, Jordan Benderoth, Jennifer K. Lee Biomolecules.2026; 16(5): 621. CrossRef
Anoikis resistance as a key driver of glioma malignancy: From ECM detachment to potential druggable targets Yuheng Zou, Chen Zou, Xiumei Huang, Yipeng Zhu, Qirui Wang Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2026; 1881(4): 189608. CrossRef
Protective effect and possible mechanisms of resveratrol in animal models of spinal cord injury: a preclinical systematic review and meta-analysis Yingchun Li, Dongping Wan, Dongliang Wang, Tao Chen, Rui Wang, Rui Tang, Tianle Chen, Shihang Cao, Bo Dong, Baohui Wang Frontiers in Immunology.2026;[Epub] CrossRef
Mitochondrial-Inflammatory Axis Dysregulation Triggers Disulfidptosis and the Multifaceted Protective Mechanism of Bisphenol A Following Spinal Cord Injury Zixing Xu, Zhechen Li, Xinhao Huang, Chuanrong Chen, Changyi Jiang, Weihong Xu Molecular Neurobiology.2026;[Epub] CrossRef
PLD3-mediated Mitophagy Attenuates Neuronal Ferroptosis and Promotes Functional Recovery after Spinal Cord Injury Xintian Ding, Bin Dai, Jiafeng Peng, Kenan Sun, Shaoze Lan, Liu Yang, Canming Ye, Shenglong Pan, Chen Wang, Xinyu Liang, Ciren Lunzhu, Chun Chen, Yunliang Zhu, Jun Li Molecular Neurobiology.2026;[Epub] CrossRef
The Therapeutic Potential of MicroRNA-21 in the Treatment of Spinal Cord Injury Ahmed Hasan, Alessio Ardizzone, Domenico Giosa, Sarah Adriana Scuderi, Elsa Calcaterra, Emanuela Esposito, Anna Paola Capra Current Issues in Molecular Biology.2025; 47(2): 70. CrossRef
Machine Learning and Experiments Revealed Key Genes Related to PANoptosis Linked to Drug Prediction and Immune Landscape in Spinal Cord Injury Bo Li, Tao Li, Yibo Cai, Junyao Cheng, Chuyue Zhang, Jianheng Liu, Keran Song, Zheng Wang, Xinran Ji Molecular Neurobiology.2025; 62(6): 7364. CrossRef
Metformin’s therapeutic potential in spinal cord injury: a systematic review and meta-analysis on locomotor recovery, neuropathic pain alleviation, and modulation of secondary injury mechanisms Mohammadhossein Vazirizadeh-Mahabadi, Amir Azimi, Mobina Yarahmadi, Hamed Zarei, Fateme Tahmasbi, Amirali Zarrin, Mahmoud Yousefifard, Vafa Rahimi-Movaghar Acta Neurochirurgica.2025;[Epub] CrossRef
Advanced Strategies in Enhancing the Hepatoprotective Efficacy of Natural Products: Integrating Nanotechnology, Genomics, and Mechanistic Insights Jitendra Patel, Harekrishna Roy, Pavan Kuma Chintamaneni, Rukmani Patel, Raghvendra Bohara ACS Biomaterials Science & Engineering.2025; 11(5): 2528. CrossRef
Navigating the complexities of spinal cord injury: an overview of pathology, treatment strategies and clinical trials Manjeet Chopra, Hemant Kumar Drug Discovery Today.2025; 30(6): 104387. CrossRef
Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury Lahanya Guha, Divya Goyal, Nidhi Singh, Mamidi Teena, Inbo Han, Hemant Kumar Molecular Neurobiology.2025; 62(10): 13763. CrossRef
A Commentary on “Transcranial Optogenetic Stimulation Promotes Corticospinal Tract Axon Regeneration to Repair Spinal Cord Injury by Activating the JAK2/STAT3 Pathway” Wu Xue, Anyuan Dai, Qinyi Liu Neurospine.2025; 22(2): 329. CrossRef
Precision Recovery After Spinal Cord Injury: Integrating CRISPR Technologies, AI-Driven Therapeutics, Single-Cell Omics, and System Neuroregeneration Răzvan-Adrian Covache-Busuioc, Corneliu Toader, Mugurel Petrinel Rădoi, Matei Șerban International Journal of Molecular Sciences.2025; 26(14): 6966. CrossRef
Disruptions in nitric oxide homeostasis, lipid peroxidation-derived oxidative stress, and antioxidant defense mechanisms in spinal cord injury: elucidating biomolecular correlates of disease severity Mohd Mursal, Irfan Hasan, Babita Tiwari, Rajesh K. Srivastava, Ganesh Yadav, Ghizal Fatima Molecular Biology Reports.2025;[Epub] CrossRef
RNA Interference and Its Key Targets for Spinal Cord Injury Therapy: What Is Known So Far? Daria Chudakova, Vladimir Kovalev, Matthew Shkap, Elizaveta Sigal, Arthur Biktimirov, Alesya Soboleva, Vladimir Baklaushev International Journal of Molecular Sciences.2025; 26(20): 9861. CrossRef
Therapeutic Effects of Photobiomodulation Therapy on Ovarian Structure and GDF9, BMP15 and BMP4 Expression in the Spinal Cord Injury Female Rat Model Shima Jahanbaz, Hamid Reza Mosleh, Hadise Taheri, Reza Mastery Farahani, Amin Karamin, Foozhan Tahmasebinia, Hooman Kazemi Mirni, Sama Abbasi, Mahbobeh Hossainpour, Hojjat-Allah Abbaszadeh Journal of Lasers in Medical Sciences.2025; 16: e12. CrossRef
The role of apoptosis in spinal cord injury: a bibliometric analysis from 1994 to 2023 Siqiao Wang, Liming Cheng Frontiers in Cellular Neuroscience.2024;[Epub] CrossRef
From hope to healing: Exploring the therapeutic potential of exosomes in spinal cord injury Nidhi Singh, Lahanya Guha, Hemant Kumar Extracellular Vesicle.2024; 3: 100044. CrossRef
Molars to Medicine: A Focused Review on the Pre-Clinical Investigation and Treatment of Secondary Degeneration following Spinal Cord Injury Using Dental Stem Cells Sandra Jenkner, Jillian Mary Clark, Stan Gronthos, Ryan Louis O’Hare Doig Cells.2024; 13(10): 817. CrossRef
Enhancing motor functional recovery in spinal cord injury through pharmacological inhibition of Dickkopf-1 with BHQ880 antibody Carlos González-Fernández, Pau González, Alfredo Maqueda, Virginia Pérez, Francisco Javier Rodríguez Biomedicine & Pharmacotherapy.2024; 176: 116792. CrossRef
Repeated intrathecal injections of peripheral nerve-derived stem cell spheroids improve outcomes in a rat model of traumatic brain injury Hae Eun Shin, Won-Jin Lee, Kwang-Sook Park, Yerin Yu, Gyubin Kim, Eun Ji Roh, Byeong Gwan Song, Joon-Hyuk Jung, Kwangrae Cho, Young-hu Ha, Young-Il Yang, Inbo Han Stem Cell Research & Therapy.2024;[Epub] CrossRef
Advancements in Antioxidant-Based Therapeutics for Spinal Cord Injury: A Critical Review of Strategies and Combination Approaches Yang-Jin Shen, Yin-Cheng Huang, Yi-Chuan Cheng Antioxidants.2024; 14(1): 17. CrossRef
Commentary on “Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury” Jeffrey Luo, Joshua B. Stein, Ki-Bum Lee Neurospine.2023; 20(2): 449. CrossRef
From the Editor-in-Chief: Featured Articles in the June 2023 Issue Inbo Han Neurospine.2023; 20(2): 413. CrossRef
Drug Repurposing for Spinal Cord Injury: Progress Towards Therapeutic Intervention for Primary Factors and Secondary Complications Lahanya Guha, Hemant Kumar Pharmaceutical Medicine.2023; 37(6): 463. CrossRef
Gut microbiota and traumatic central nervous system injuries: Insights into pathophysiology and therapeutic approaches Lahanya Guha, Tejas Girish Agnihotri, Aakanchha Jain, Hemant Kumar Life Sciences.2023; 334: 122193. CrossRef
Tibolone Improves Locomotor Function in a Rat Model of Spinal Cord Injury by Modulating Apoptosis and Autophagy Stephanie Sánchez-Torres, Carlos Orozco-Barrios, Hermelinda Salgado-Ceballos, Julia J. Segura-Uribe, Christian Guerra-Araiza, Ángel León-Cholula, Julio Morán, Angélica Coyoy-Salgado International Journal of Molecular Sciences.2023; 24(20): 15285. CrossRef
A spinal cord injury (SCI) is a destructive event that causes a permanent deficit in neurological function because of poor regenerative potential. Transplantation therapies have attracted attention for restoration of the injured spinal cord, and transplantation of neural precursor cells (NPCs) has been studied worldwide. Several groups have demonstrated functional recovery via this therapeutic intervention due to the multiple beneficial effects of NPC transplantation, such as reconstruction of neuronal circuits, remyelination of axons, and neuroprotection by trophic factors. Our group developed a method to induce NPCs from human induced pluripotent stem cells (hiPSCs) and established a transplantation strategy for SCI. Functional improvement in SCI animals treated with hiPSC-NPCs was observed, and the safety of transplanting these cells was evaluated from multiple perspectives. With selection of a safe cell line and pretreatment of the cells to encourage maturation and differentiation, hiPSC-NPC transplantation therapy is now in the clinical phase of testing for subacute SCI. In addition, a research challenge will be to expand the efficacy of transplantation therapy for chronic SCI. More comprehensive strategies involving combination treatments are required to treat this problematic situation.
Citations
Citations to this article as recorded by
A Soft, Flexible Implant for Wireless Photothermal–Pyroelectric Neurostimulation Jiang Wu, Minmin Mao, Beltzane Garcia Cirera, Hao Ye, Xiangzhong Chen, Josep Puigmartí‐Luis, Ni Qin, Salvador Pané Advanced Science.2026;[Epub] CrossRef
Stem Cell-Based Approaches for Spinal Cord Injury: The Promise of iPSCs Chih-Wei Zeng Biology.2025; 14(3): 314. CrossRef
Cell replacement with stem cell-derived retinal ganglion cells from different protocols Ziming Luo, Kun-Che Chang Neural Regeneration Research.2024; 19(4): 807. CrossRef
Transplantation of Predegenerated Peripheral Nerves after Complete Spinal Cord Transection in Rats: Effect of Neural Precursor Cells and Pharmacological Treatment with the Sulfoglycolipid Tol-51 Alejandro Arriero-Cabañero, Elisa García-Vences, Stephanie Sánchez-Torres, Sergio Aristizabal-Hernandez, Concepción García-Rama, Enrique Pérez-Rizo, Alfonso Fernández-Mayoralas, Israel Grijalva, Vinnitsa Buzoianu-Anguiano, Ernesto Doncel-Pérez, Jörg Mey Cells.2024; 13(16): 1324. CrossRef
Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction Sung Jun Hong, Minsung Bock, Songzi Zhang, Seong Bae An, Inbo Han International Journal of Molecular Sciences.2024; 25(15): 8540. CrossRef
Repeated intrathecal injections of peripheral nerve-derived stem cell spheroids improve outcomes in a rat model of traumatic brain injury Hae Eun Shin, Won-Jin Lee, Kwang-Sook Park, Yerin Yu, Gyubin Kim, Eun Ji Roh, Byeong Gwan Song, Joon-Hyuk Jung, Kwangrae Cho, Young-hu Ha, Young-Il Yang, Inbo Han Stem Cell Research & Therapy.2024;[Epub] CrossRef
Multimodal therapy strategy based on a bioactive hydrogel for repair of spinal cord injury Eun Ji Roh, Da-Seul Kim, Jun Hyuk Kim, Chang Su Lim, Hyemin Choi, Su Yeon Kwon, So-Yeon Park, Jun Yong Kim, Hyun-Mun Kim, Dong-Youn Hwang, Dong Keun Han, Inbo Han Biomaterials.2023; 299: 122160. CrossRef
Co-Administration of Resolvin D1 and Peripheral Nerve-Derived Stem Cell Spheroids as a Therapeutic Strategy in a Rat Model of Spinal Cord Injury Seung-Young Jeong, Hye-Lan Lee, SungWon Wee, HyeYeong Lee, GwangYong Hwang, SaeYeon Hwang, SolLip Yoon, Young-Il Yang, Inbo Han, Keung-Nyun Kim International Journal of Molecular Sciences.2023; 24(13): 10971. CrossRef
Transplantation of Chemical Compound-Induced Cells from Human Fibroblasts Improves Locomotor Recovery in a Spinal Cord Injury Rat Model Toshihiro Kurahashi, Chiyoko Nishime, Eiko Nishinaka, Yuji Komaki, Fumiko Seki, Koji Urano, Yoshinori Harada, Toshikazu Yoshikawa, Ping Dai International Journal of Molecular Sciences.2023; 24(18): 13853. CrossRef
Traumatic spinal cord injury (SCI) disrupts the spinal cord vasculature resulting in ischemia, amplification of the secondary injury cascade and exacerbation of neural tissue loss. Restoring functional integrity of the microvasculature to prevent neural loss and to promote neural repair is an important challenge and opportunity in SCI research. Herein, we summarize the course of vascular injury and repair following SCI and give a comprehensive overview of current experimental therapeutic approaches targeting spinal cord microvasculature to diminish ischemia and thereby facilitate neural repair and regeneration. A systematic review of the published literature on therapeutic approaches to promote vascular repair after experimental SCI was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. The MEDLINE databases PubMed, Embase, and OVID MEDLINE were searched using the keywords “spinal cord injury,” “angiogenesis,” “angiogenesis inducing agents,” “tissue engineering,” and “rodent subjects.” A total of 111 studies were identified through the search. Five main therapeutic approaches to diminish hypoxia-ischemia and promote vascular repair were identified as (1) the application of angiogenic factors, (2) genetic engineering, (3) physical stimulation, (4) cell transplantation, and (5) biomaterials carrying various factor delivery. There are different therapeutic approaches with the potential to diminish hypoxia-ischemia and promote vascular repair after experimental SCI. Of note, combinatorial approaches using implanted biomaterials and angiogenic factor delivery appear promising for clinical translation.
Citations
Citations to this article as recorded by
Synergistic aligned neuronal and vascular growth inside 3D-PEG-Anisogels utilizing a triple-co-culture Céline Bastard, Philip Pietryszek, Hela Uplegger, Matthias Mork, Jose Luis Gerardo Nava, Tamás Haraszti, Laura De Laporte Materials Today Bio.2026; 36: 102737. CrossRef
Optimizing deferoxamine delivery through the skin for pressure ulcers Katharina S. Berryman, Maria Gracia Mora Pinos, Amy Skarsfeldt, Lulejeta Latifi, Pedro Mora Pinos, Kellen Chen, Geoffrey C. Gurtner Expert Opinion on Drug Delivery.2026; 23(4): 621. CrossRef
Spatiotemporal PET imaging of P2X7R-driven neuroinflammation using [18F]GSK1482160 after experimental acute spinal cord injury in mice Jiaxing Shi, Kun Wang, Yuyi Hou, Sirui Wu, Yifan Qiu, Xiang Liu, Lihua Huang, Shiyanjin Zhang, Hongjun Jin, Hai Lu Brain, Behavior, and Immunity.2026; 134: 106279. CrossRef
Sustained nitric oxide production by engineered E. coli remodels the tumor microenvironment and potentiates immunotherapy Shuyu Xu, Tianjiao Zhang, Yang Song, Mengxin Wang, Ruiqi Wu, Mofan Li, Haonan Wang, Xinxin Xie, Qingfeng Chen, Xiaotu Ma, Xiaolong Liang Nature Biotechnology.2026;[Epub] CrossRef
Network-guided identification and in vitro/in vivo validation of Withaferin A as an inhibitor of nuclear factor kappa B for spinal cord injury repair Chenghu Xie, Cunxin Zhang, Ying Zhang, Liyi Chen, Xiao He, Xinzhou Xie, Kang Li, Xiaodong Wang, Chaoliang Lv Phytomedicine.2026; 158: 158380. CrossRef
Spinal Cord Blood Perfusion Deficit is Associated with Clinical Impairment after Spinal Cord Injury Anna Lebret, Sabina Frese, Simon Lévy, Armin Curt, Virginie Callot, Patrick Freund, Maryam Seif Journal of Neurotrauma.2025; 42(3-4): 280. CrossRef
Identification of a Therapeutic Window for Neurovascular Unit Repair after Experimental Spinal Cord Injury Vanessa Hubertus, Lea Meyer, Lilly Waldmann, Laurens Roolfs, Nima Taheri, Katharina Kersting, Emily von Bronewski, Melina Nieminen-Kelhä, Irina Kremenetskaia, Christian Uhl, Kim C. Fiedler, Jan-Erik Ode, Andre Rex, Harald Prüß, Asylkhan Rakhymzhan, Anja E Journal of Neurotrauma.2025; 42(3-4): 212. CrossRef
Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury Christian J. Entenmann, Emily J. von Bronewski, Lilly Waldmann, Lea Meyer, Katharina Kersting, Laurens T. Roolfs, Lasse M. Schleker, Melina Nieminen-Kelhä, Irina Kremenetskaia, Frank L. Heppner, Michael G. Fehlings, Peter Vajkoczy, Vanessa Hubertus Brain and Spine.2025; 5: 104191. CrossRef
AO Spine Clinical Practice Recommendations for the Surgical Management of Acute Traumatic Spinal Cord Injury: Contemporary Concepts Vanessa Hubertus, Jetan H. Badhiwala, Nader Hejrati, Aria Nouri, Paula V. Ter Wengel, Farzin Farahbakhsh, Christoph Hofstetter, Chris J. Neal, Mario Ganau, Nitin Agarwal, Paul Arnold, Paul Koljonen, James Harrop, Bizhan Aarabi, James Guest, Ricardo Rodrig Global Spine Journal.2025; 15(8): 3572. CrossRef
Quercetin promotes angiogenesis and protects the blood-spinal cord barrier structure after spinal cord injury by targeting the PI3K/Akt signaling pathway Xinfang Liu, Xuhua Liu, Sidong Luo, Di Chen, Jinbo Lin, Man Xiong, Lei Yang, Kaifan Li, Dawei Sun, Lina Wei, Sheng Luo, Yeyang Wang Journal of Translational Medicine.2025;[Epub] CrossRef
Stem cell therapy for locomotion recovery and neuropathic pain alleviation in spinal cord injury: an umbrella review and meta-analysis Amir Azimi, Amirmohammad Toloui, Mohammadhossein Mozafarybazargany, Mohammad Kiah, Hamed Zarei, Parsa Paridari, Sajjad Jabermoradi, Donya Pourkand, Hamzah Adel Ramawad, Alexander R. Vaccaro, Mostafa Hosseini, Mahmoud Yousefifard, Vafa Rahimi-Movaghar Spinal Cord.2025; 63(8): 393. CrossRef
Peptide-conjugated aligned silk fiber simultaneously promotes angiogenesis and neurogenesis for spinal cord injury therapy Ke Jian, Chaoyong He, Ziqiang Wang, Yajun Li, Can Zhang, Liyang Shi, Jianwu Dai Chemical Engineering Journal.2025; 523: 168679. CrossRef
Neurovascular dynamics in the spinal cord from development to pathophysiology Carmen Ruiz de Almodovar, Sebastian Dupraz, Dario Bonanomi Neuron.2025; 113(24): 4134. CrossRef
Endothelial ephrin-B2 knockdown increases post-traumatic disruption of the blood-spinal cord barrier following spinal cord injury Katharina Kersting, Emily J. von Bronewski, Laurens T. Roolfs, Lea Meyer, Lilly Waldmann, Melina Nieminen-Kelhä, Irina Kremenetskaia, Anja Nitzsche, Andre Rex, Harald Prüß, Ralf Adams, Frank L. Heppner, Michael G. Fehlings, Peter Vajkoczy, Vanessa Hubertu Neurobiology of Disease.2025; 217: 107168. CrossRef
A Comprehensive Overview of Spinal Cord Injury (SCI) Experimental Models Modinat Olushanu Premier Journal of Neuroscience.2025;[Epub] CrossRef
AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling Xin Miao, Junqing Lin, Ang Li, Tao Gao, Tiexin Liu, Junjie Shen, Yi Sun, Jiabao Wei, Bingbo Bao, Xianyou Zheng Experimental Neurology.2024; 375: 114739. CrossRef
AO Spine/Praxis Clinical Practice Guidelines for the Management of Acute Spinal Cord Injury: An Introduction to a Focus Issue Brian K. Kwon, Lindsay A. Tetreault, Nathan Evaniew, Andrea C. Skelly, Michael G. Fehlings Global Spine Journal.2024; 14(3_suppl): 5S. CrossRef
Intranasal delivery of small extracellular vesicles from specific subpopulation of mesenchymal stem cells mitigates traumatic spinal cord injury Yi Sun, Jinyun Zhao, Quanbo Liu, Yan Xu, Yiming Qin, Rundong He, Lifu Zheng, Yong Xie, Chengjun Li, Tianding Wu, Yong Cao, Chunyue Duan, Hongbin Lu, Jianzhong Hu Journal of Controlled Release.2024; 369: 335. CrossRef
Spinal Cord Injury Management Based on Microglia-Targeting Therapies Thomas Gabriel Schreiner, Oliver Daniel Schreiner, Romeo Cristian Ciobanu Journal of Clinical Medicine.2024; 13(10): 2773. CrossRef
Stem Cell and Regenerative Therapies for the Treatment of Osteoporotic Vertebral Compression Fractures Songzi Zhang, Yunhwan Lee, Yanting Liu, Yerin Yu, Inbo Han International Journal of Molecular Sciences.2024; 25(9): 4979. CrossRef
Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction Sung Jun Hong, Minsung Bock, Songzi Zhang, Seong Bae An, Inbo Han International Journal of Molecular Sciences.2024; 25(15): 8540. CrossRef
Innovative Strategies in 3D Bioprinting for Spinal Cord Injury Repair Daniel Youngsuk Kim, Yanting Liu, Gyubin Kim, Seong Bae An, Inbo Han International Journal of Molecular Sciences.2024; 25(17): 9592. CrossRef
p53/HIF-1α regulates neuronal aging and autophagy in spinal cord ischemia/reperfusion injury Xingzhen Liu, Jia Wang, Kangping Shen, Wenjie Jin Mechanisms of Ageing and Development.2024; 222: 112000. CrossRef
Co-Administration of Resolvin D1 and Peripheral Nerve-Derived Stem Cell Spheroids as a Therapeutic Strategy in a Rat Model of Spinal Cord Injury Seung-Young Jeong, Hye-Lan Lee, SungWon Wee, HyeYeong Lee, GwangYong Hwang, SaeYeon Hwang, SolLip Yoon, Young-Il Yang, Inbo Han, Keung-Nyun Kim International Journal of Molecular Sciences.2023; 24(13): 10971. CrossRef
The Importance of Vascular Repair as the First Step in Spinal Cord Injury Treatment: Commentary on “Therapeutic Approaches Targeting Vascular Repair After Experimental Spinal Cord Injury: A Systematic Review of the Literature” Kyoung-Tae Kim Neurospine.2022; 19(4): 976. CrossRef
Objective To develop a nomogram for the prediction of tracheostomy in patients with traumatic cervical spinal cord injury (TCSCI).
Methods A total of 689 TCSCI patients were included in our study. First, the variable selection was performed using between-group comparisons and LASSO regression analysis. Second, a multivariate logistic regression analysis (MLRA) with a step-by-step method was performed. A nomogram model was developed based on the MLRA. Finally, the model was validated on the training set and validation set.
Results The nomogram prediction model incorporated 5 predictors, including smoking history, dislocation, thoracic injury, American Spinal Injury Association (ASIA) grade, and neurological level of injury (NLI). The area under curve in the training group and in the validation group were 0.883 and 0.909, respectively. The Hosmer-Lemeshow test result was p = 0.153. From the decision curve analysis curve, the model performed well and was feasible to make beneficial clinical decisions.
Conclusion The nomogram combining dislocation, thoracic injury, ASIA grade A, NLI, and smoking history was validated as a reliable model for the prediction of tracheostomy.
Citations
Citations to this article as recorded by
Development and validation of a nomogram for predicting tracheostomy risk in traumatic cervical spinal cord injury Weiting Chen, Xiaoshuang Jiang, Xixi Guo, Jiuzhou Lin, Min Tang, Nanlin Dou Frontiers in Neurology.2026;[Epub] CrossRef
Management of acute cervical spinal cord injury in the non‐specialist intensive care unit: a narrative review of current evidence M. D. Wiles, I. Benson, L. Edwards, R. Miller, F. Tait, A. Wynn‐Hebden Anaesthesia.2024; 79(2): 193. CrossRef
Traumatic spinal cord injury in South Korea for 13 years (2008–2020) Sung Hyun Noh, Eunyoung Lee, Kyoung-Tae Kim, Sang Hyun Kim, Pyung Goo Cho Scientific Reports.2024;[Epub] CrossRef
Co-Administration of Resolvin D1 and Peripheral Nerve-Derived Stem Cell Spheroids as a Therapeutic Strategy in a Rat Model of Spinal Cord Injury Seung-Young Jeong, Hye-Lan Lee, SungWon Wee, HyeYeong Lee, GwangYong Hwang, SaeYeon Hwang, SolLip Yoon, Young-Il Yang, Inbo Han, Keung-Nyun Kim International Journal of Molecular Sciences.2023; 24(13): 10971. CrossRef
First
Prev
