Lithium Chloride Reinforces the Regeneration-Promoting Effect of Chondroitinase ABC on Rubrospinal Neurons after Spinal Cord Injury
Abstract
After spinal cord injury, enzymatic digestion of chondroitin sulfate proteoglycans promotes axonal regeneration of central nervous system neurons across the lesion scar. We examined whether chondroitinase ABC (ChABC) promotes the axonal regeneration of rubrospinal tract (RST) neurons following injury to the spinal cord. The effect of a GSK-3beta inhibitor, lithium chloride (LiCl), on the regeneration of axotomized RST neurons was also assessed. Adult rats received a unilateral hemisection at the seventh cervical spinal cord segment (C7). Four weeks after different treatments, regeneration of RST axons across the lesion scar was examined by injection of Fluoro-Gold at spinal segment T2, and locomotor recovery was studied by a test of forelimb usage. Injured RST axons did not regenerate spontaneously after spinal cord injury, and intraperitoneal injection of LiCl alone did not promote the regeneration of RST axons. Administration of ChABC at the lesion site enhanced the regeneration of RST axons by 20%. Combined treatment of LiCl together with ChABC significantly increased the regeneration of RST axons to 42%. Animals receiving combined treatment used both forelimbs together more often than animals that received sham or single treatment. Immunoblotting and immunohistochemical analysis revealed that LiCl induced the expression of inactive GSK-3beta as well as the upregulation of Bcl-2 in injured RST neurons. These results indicate that in vivo, LiCl inhibits GSK-3beta and reinforces the regeneration-promoting function of ChABC through a Bcl-2-dependent mechanism. Combined use of LiCl together with ChABC could be a novel treatment for spinal cord injury.
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Lithium treatment was shown in rodents to facilitate enzymatic CSPG digestion.
“lithium treatment was shown in rodents to facilitate enzymatic CSPG digestion.71, 72”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [71]
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- Authors
- Yick, L.-W., So, K.-F., Cheung, P.-T., & Wu, W.-T.
- Affiliations
- University of Hong Kong (HK)
- Department of Anatomy, The University of Hong Kong, Hong Kong.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2004-07
- Volume
- 21
- Issue
- 7
- Pages
- 932-943
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- OpenAlex
- W1521494846
- Cited by
- 108
- References
- 51
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 7 · 2014: 3 · 2013: 9 · 2012: 5
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- University of Hong Kong
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- spinal cord injury, chondroitinase ABC, lithium chloride, GSK-3β inhibition, axon regeneration, chondroitin sulfate proteoglycans, Bcl-2, locomotor recovery, hemisection, axotomy
- MeSH terms
- Adjuvants, Immunologic, Animals, Cervical Vertebrae, Drug Synergism, Image Processing, Computer-Assisted, Immunohistochemistry, Motor Activity, Nerve Regeneration, Neurons, Spinal Cord Injuries, Blotting, Western, Rats, Sprague-Dawley, Lithium Chloride, Proto-Oncogene Proteins c-bcl-2, Chondroitin ABC Lyase, Recovery of Function, Rats
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