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Intraspinal microinjection of chondroitinase ABC following injury promotes axonal regeneration out of a peripheral nerve graft bridge
Journal article   Open access   Peer reviewed

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

Veronica J Tom and John D Houlé
Experimental neurology, v 211(1)
May 2008
PMID: 18353313
url
https://doi.org/10.1016/j.expneurol.2008.01.021View
Published, Version of Record (VoR) Open

Abstract

Recovery of Function - drug effects Ectodysplasins - metabolism Axons - drug effects Chondroitin ABC Lyase - administration & dosage Rats Axons - physiology Glial Fibrillary Acidic Protein - metabolism Rats, Sprague-Dawley Spinal Cord Injuries - pathology Animals Tibial Nerve - transplantation Nerve Regeneration - drug effects Female Injections, Spinal - methods Spinal Cord Injuries - physiopathology Spinal Cord Injuries - therapy
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 demonstrate 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.

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