Degradation of chondroitin sulfate proteoglycans potentiates transplant-mediated axonal remodeling and functional recovery after spinal cord injury in adult rats
| Autor: | Haining Dai, Byung Gon Kim, Barbara S. Bregman, Marietta McAtee, James V. Lynskey |
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| Rok vydání: | 2006 |
| Předmět: |
Diagnostic Imaging
Serotonin Time Factors animal structures Cord Cell Transplantation Biotin Cell Count Chondroitin ABC Lyase Motor Activity Biology Inhibitory postsynaptic potential Article Rats Sprague-Dawley Lesion medicine Animals Spinal cord injury Spinal Cord Injuries Behavior Animal General Neuroscience Regeneration (biology) Dextrans Recovery of Function medicine.disease Immunohistochemistry Axons Rats Cell biology Enzyme Activation Transplantation Disease Models Animal surgical procedures operative medicine.anatomical_structure Animals Newborn Chondroitin Sulfate Proteoglycans nervous system Phosphopyruvate Hydratase Cervical enlargement Female medicine.symptom Forelimb Neuroscience |
| Zdroj: | The Journal of Comparative Neurology. 497:182-198 |
| ISSN: | 1096-9861 0021-9967 |
| DOI: | 10.1002/cne.20980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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