Cited by 108Nerve injury and regenerationSpinal Cord Injury ResearchNeurogenesis and neuroplasticity mechanisms

Lithium Chloride Reinforces the Regeneration-Promoting Effect of Chondroitinase ABC on Rubrospinal Neurons after Spinal Cord Injury

Yick, Leung-Wah, So, Kwok-Fai, Cheung, Pik-To, Wu, Wu-Tian·2004·Journal of Neurotrauma

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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Crossref · 10.1089/0897715041526221

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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
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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