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Chondroitinase ABC promotes compensatory sprouting of the intact corticospinal tract and recovery of forelimb function following unilateral pyramidotomy in adult mice
Author(s) -
Starkey Michelle L.,
Bartus Katalin,
Barritt Andrew W.,
Bradbury Elizabeth J.
Publication year - 2012
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12017
Subject(s) - corticospinal tract , forelimb , sprouting , spinal cord , neuroscience , grey matter , superior colliculus , spinal cord injury , white matter , brainstem , anatomy , chemistry , biology , medicine , diffusion mri , botany , magnetic resonance imaging , radiology
Chondroitin sulphate proteoglycans ( CSPG s) are extracellular matrix molecules whose inhibitory activity is attenuated by the enzyme chondroitinase ABC ( C h ABC ). Here we assess whether CSPG degradation can promote compensatory sprouting of the intact corticospinal tract ( CST ) following unilateral injury and restore function to the denervated forelimb. Adult C 57 BL /6 mice underwent unilateral pyramidotomy and treatment with either C h ABC or a vehicle control. Significant impairments in forepaw symmetry were observed following pyramidotomy, with injured mice preferentially using their intact paw during spontaneous vertical exploration of a cylinder. No recovery on this task was observed in vehicle‐treated mice. However, C h ABC ‐treated mice showed a marked recovery of function, with forelimb symmetry fully restored by 5 weeks post‐injury. Functional recovery was associated with robust sprouting of the uninjured CST , with numerous axons observed crossing the midline in the brainstem and spinal cord and terminating in denervated grey matter. CST fibres in the denervated side of the spinal cord following C h ABC treatment were closely associated with the synaptic marker v G lut1. Immunohistochemical assessment of chondroitin‐4‐sulphate revealed that CSPG s were heavily digested around lamina X , alongside midline crossing axons and in grey matter regions where sprouting axons and reduced peri‐neuronal net staining was observed. Thus, we demonstrate that CSPG degradation promotes midline crossing and reinnervation of denervated target regions by intact CST axons and leads to restored function in the denervated forepaw. Enhancing compensatory sprouting using C h ABC provides a route to restore function that could be applied to disorders such as spinal cord injury and stroke.