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PMID: 16705682 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Degradation of chondroitin sulfate proteoglycans potentiates transplant-mediated axonal remodeling and functional recovery after spinal cord injury in adult rats.

The Journal of comparative neurology ·Vol. 497 ·No. 2 ·2006-07-10 ·Pages 182-98

Kim BG, Dai HN, Lynskey JV, McAtee M, Bregman BS

Abstract

Transplantation of growth-permissive cells or tissues was used to bridge a lesion cavity and induce axonal growth in experimental spinal cord injury (SCI). Axonal interactions between host and transplant may be affected by upregulation of inhibitory chondroitin sulfate proteoglycans (CSPGs) following various transplantation strategies. The extent of axonal growth and functional recovery after transplantation of embryonic spinal cord tissue decreases in adult compared to neonatal host. We hypothesized that CSPGs contribute to the decrease in the extent to which transplant supports axonal remodeling and functional recovery. Expression of CSPGs increased after overhemisection SCI in adult rats but not in neonates. Embryonic spinal cord transplant was surrounded by CSPGs deposited in host cord, and the interface between host and transplant seemed to contain a large amount of CSPGs. Intrathecally delivered chondroitinase ABC (C'ase) improved recovery of distal forelimb usage and skilled motor behavior after C4 overhemisection injury and transplantation in adults. This behavioral recovery was accompanied by an increased amount of raphespinal axons growing into the transplant, and raphespinal innervation to the cervical motor region was promoted by C'ase plus transplant. Moreover, C'ase increased the number of transplanted neurons that grew axons to the host cervical enlargement, suggesting that degradation of CSPGs supports remodeling not only of host axons but also axons from transplanted neurons. Our results suggest that CSPGs constitute an inhibitory barrier to prevent axonal interactions between host and transplant in adults, and degradation of the inhibitory barrier can potentiate transplant-mediated axonal remodeling and functional recovery after SCI.

MeSH Terms
Animals Animals, Newborn Axons/drug effects,physiology Behavior, Animal/drug effects,physiology Biotin/analogs & derivatives,pharmacokinetics Cell Count/methods Cell Transplantation Chondroitin ABC Lyase/administration & dosage Chondroitin Sulfate Proteoglycans/metabolism Dextrans/pharmacokinetics Diagnostic Imaging/methods Disease Models, Animal Enzyme Activation/drug effects Female Immunohistochemistry/methods Motor Activity/drug effects,physiology Phosphopyruvate Hydratase/metabolism Rats Rats, Sprague-Dawley Recovery of Function/drug effects,physiology Serotonin/metabolism Spinal Cord Injuries/metabolism,physiopathology,surgery Time Factors
Chemicals
Chondroitin Sulfate Proteoglycans Dextrans biotinylated dextran amine Serotonin Biotin Phosphopyruvate Hydratase Chondroitin ABC Lyase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kim Byung G
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
Dai Hai-Ning
Lynskey James V
McAtee Marietta
Bregman Barbara S
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Article Info
Journal
The Journal of comparative neurology
Abbr.
J Comp Neurol
ISSN
0021-9967
DOI
10.1002/cne.20980
Published
2006-07-10
Pages
182-98
Language
English
Region
United States
NLM ID
0406041
PMCID
PMC2570641
Subset
IM
Grants
NINDS NIH HHS · R01 NS027054-16 · United States
NINDS NIH HHS · NS27054 · United States
NINDS NIH HHS · R01 NS027054-15 · United States
NINDS NIH HHS · R01 NS027054 · United States
NINDS NIH HHS · R01 NS027054-14 · United States
External Links
PubMed source DOI: 10.1002/cne.20980 PMC Full Text View journal details
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