Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus after cervical spinal cord injury.
Upregulation of extracellular chondroitin sulfate proteoglycans (CSPGs) after CNS injuries contributes to the impediment of functional recovery by restricting both axonal regeneration and synaptic plasticity. In the present study, the effect of degrading CSPGs with the application of the bacterial enzyme chondroitinase ABC (chABC) into the cuneate nucleus of rats partially denervated of forepaw dorsal column axons was examined. A dorsal column transection between the C6-C7 dorsal root entry zones was followed immediately by an ipsilateral brainstem injection of either chABC or a bacterial-derived control enzyme [penicillinase (P-ase)] and then subsequently (1 week later) followed with a second brainstem enzyme injection and cholera toxin B subunit (CTB) tracer injection into the ipsilateral forepaw digits and pads. After 1 additional week, the rats underwent electrophysiological receptive field mapping of the cuneate nucleus and/or anatomical evaluation. Examination of the brainstems of rats from each group revealed that CSPGs had been reduced after chABC treatment. Importantly, in the chABC-treated rats (but not in the P-ase controls), a significantly greater area of the cuneate nucleus was occupied by physiologically active CTB traced forepaw afferents that had been spared by the initial cord lesion. These results demonstrate, for the first time, a functional change directly linked to anatomical evidence of sprouting by spinal cord afferents after chABC treatment.
Massey
James M
JM
School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA.
Hubscher
Charles H
CH
Wagoner
Michelle R
MR
Decker
Julie A
JA
Amps
Jeremy
J
Silver
Jerry
J
Onifer
Stephen M
SM
D000344:Afferent Pathways / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D002574:Cervical Vertebrae / Q000187:drug effects / Q000201:enzymology*; D019765:Chondroitin ABC Lyase / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000201:enzymology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000201:enzymology; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000201:enzymology*
D011508:Chondroitin Sulfate Proteoglycans; D019765:Chondroitin ABC Lyase