Journal
EXPERIMENTAL NEUROLOGY
Volume 228, Issue 1, Pages 149-156Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2010.12.023
Keywords
Spinal cord injury; Red nucleus; Proteoglycan; Atrophy; Repair neuroprotection
Categories
Funding
- U.K. Medical Research Council
- International Spinal Research Trust
- MRC [G1002055, G120/818] Funding Source: UKRI
- Medical Research Council [G120/818, G1002055] Funding Source: researchfish
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Degradation of extracellular matrix chondroitin sulphate proteoglycans (CSPGs) using Chondroitinase ABC (ChABC) is a promising strategy for the treatment of spinal cord injury, with potent effects on promoting functional recovery and anatomical repair in spinal injured animals. We have previously demonstrated that ChABC treatment prevents atrophy of corticospinal projection neurons following spinal injury in adult YFP-H mice. Here, we investigate whether ChABC-mediated repair of the cell body extends to rubrospinal projection neurons (RSNs), whether neuroprotective effects can be sustained long-term and importantly, whether delayed treatment with ChABC can reverse chronic atrophy. Adult YFP-H mice underwent unilateral rubrospinal tract transection and were treated with ChABC or a control enzyme, delivered either acutely post-injury or after a one month delay. Eight weeks following injury and control treatment, RSNs in the injured red nucleus, identified by YFP label and NeuN immunoreactivity, showed severe atrophy, with similar to 40% loss of mean cell area compared to uninjured neurons in the contralateral red nucleus. Both acute and delayed treatment with ChABC promoted a significant rescue of injured RSNs, restoring cell area to similar to 80% and similar to 70%, respectively, of that in uninjured neurons. Thus, we demonstrate for the first time that CSPG degradation in the injured spinal cord not only promotes sustained rescue of cell atrophy when delivered acutely but can also reverse chronic atrophy in descending projection neurons. Thus, modulation of the extracellular matrix can mediate neuroprotective effects both early and late after spinal cord injury. (C) 2011 Elsevier Inc. All rights reserved.
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