Valproic acid-mediated neuroprotection and neurogenesis after spinal cord injury: from mechanism to clinical potential
Abstract
Spinal cord injury (SCI) is difficult to treat because of secondary injury. Valproic acid (VPA) is clinically approved for mood stabilization, but also counteracts secondary damage to functionally rescue SCI in animal models by improving neuroprotection and neurogenesis via inhibition of HDAC and GSK-3. However, a comprehensive review summarizing the therapeutic benefits and mechanisms of VPA for SCI and the issues affecting clinical trials is lacking, limiting future research on VPA and impeding its translation into clinical therapy for SCI. This article presents the current status of VPA treatment for SCI, emphasizing interactions between enhanced neuroprotection and neurogenesis. Crucial issues are discussed to optimize its clinical potential as a safe and effective treatment for SCI.
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Synthetic sex hormones such as DES, anticonvulsants such as valproic acid, and antidepressants such as citalopram are relevant pharmaceuticals; natural steroids such as testosterone and analogues can have neurotoxic effects at pathologically elevated concentrations.
“Synthetic sex hormones such as DES are particularly relevant, but so are anticonvulsants such as valproic acid (VPA) and antidepressants such as citalopram. Natural steroids such as testosterone and their analogues can also have neurotoxic effects in pathologically elevated concentrations (Chu et al., 2015; Pang and Han, 2012; Sass and Wörtwein, 2012; Soyer-Gobillard et al., 2025).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Chu et al., 2015
Cites
Chen, P. S., Wang, C.-C., Bortner, C. D., Peng, G.-S., Wu, X., Pang, H., Lu, R.-B., Gean, P.-W., Chuang, D.-M., & Hong, J.-S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.06.053 · Cited by 262 · see citing works
Deinhardt, K., & Chao, M. V. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-45106-5_5 · Cited by 147 · see citing works
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Chen, S., Ye, J., Chen, X., Shi, J., Wu, W., Lin, W., Lin, W., Li, Y., Fu, H., & Li, S. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1193-6 · Cited by 315 · see citing works
Masuch, A., Shieh, C., van Rooijen, N., van Calker, D., & Biber, K. (2016) · Glia · doi:10.1002/glia.22904 · Cited by 81 · see citing works
Jocsak, G., Kiss, D. S., Alymbaeva, D., Diebald, A., Zsarnovszky, A., Heinzlmann, A., & Bartha, T. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1821381 · Cited by 1 · see citing works
“Natural steroids such as testosterone and their analogues can also have neurotoxic effects in pathologically elevated concentrations (Chu et al., 2015; Pang and Han, 2012; Sass and Wörtwein, 2012; Soyer-Gobillard et al., 2025).”
- Authors
- Chu, T., Zhou, H., Lu, L., Kong, X., Wang, T., Pan, B., & Feng, S.
- Affiliations
- Tianjin Medical University General Hospital (CN)
- Nankai University (CN)
- Venue
- Regenerative Medicine
- Publisher
- Informa UK Limited
- Published
- 2014-12-08
- Volume
- 10
- Issue
- 2
- Pages
- 193-209
- ISSN
- 1746-0751 (ISSN-L)
- 1746-076X
- OpenAlex
- W2011933865
- Cited by
- 49
- References
- 2
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 2
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regenerative Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81330042)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- valproic acid, spinal cord injury, neuroprotection, neurogenesis, histone deacetylase inhibition, GSK3 inhibition, secondary injury, clinical translation, drug safety
- MeSH terms
- Neuroprotection, Animals, Clinical Trials as Topic, Densitometry, Enzyme Inhibitors, Humans, Inflammation, Spinal Cord, Spinal Cord Injuries, Valproic Acid, Neurites, Cell Death, Neuroprotective Agents, Models, Animal, Glycogen Synthase Kinase 3, Green Fluorescent Proteins, Mice, Rats, Neurogenesis, Histone Deacetylase Inhibitors
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