4.7 Article

Intraspinal microinjection of chondroitinase ABC following injury promotes axonal regeneration out of a peripheral nerve graft bridge

Journal

EXPERIMENTAL NEUROLOGY
Volume 211, Issue 1, Pages 315-319

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2008.01.021

Keywords

spinal cord injury; chondroitinase ABC; peripheral nerve graft; regeneration; chondroitin sulfate proteoglycan; glial scar

Categories

Funding

  1. NINDS NIH HHS [R37 NS026380, NS 26380, R37 NS026380-21, R01 NS026380] Funding Source: Medline

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Chondroitin sulfate proteoglycans (CSPG) within the glial scar formed after central nervous system (CNS) injury are thought to play a crucial role in regenerative failure. We previously showed that delivery of the CSPG-digesting enzyme chondroitinase ABC (ChABC) via an osmotic minipump allowed axonal regeneration and functional recovery in a peripheral nerve graft (PNG)-bridging model. In this study, we sought to overcome the technical limitations associated with minipumps by microinjecting ChABC directly into the distal lesion site in the PN bridging model. Microinjection of ChABC immediately rostral and caudal to an injury site resulted in extensive CSPG digestion. We also dernonstrate that this delivery technique is relatively atraumatic and does not result in a noticeable inflammatory response. Importantly, microinjections of ChABC into the lesion site permitted more regenerating axons to exit a PNG and reenter spinal cord tissue than saline injections. These results are similar to our previous findings when ChABC was delivered via a minipump and suggest that microinjecting ChABC is an effective method of delivering the potentially therapeutic enzyme directly to an injury site. (C) 2008 Elsevier Inc. All rights reserved.

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