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HERO ID
4461294
Reference Type
Journal Article
Title
Botulinum neurotoxin A promotes functional recovery after peripheral nerve injury by increasing regeneration of myelinated fibers
Author(s)
Cobianchi, S; Jaramillo, J; Luvisetto, S; Pavone, F; Navarro, X
Year
2017
Is Peer Reviewed?
1
Journal
Neuroscience
ISSN:
0306-4522
EISSN:
1873-7544
Volume
359
Page Numbers
82-91
Language
English
PMID
28716587
DOI
10.1016/j.neuroscience.2017.07.011
Web of Science Id
WOS:000408401100008
Abstract
The injection of safe doses of botulinum neurotoxin A (BoNT/A) have been reported to be useful for the treatment of neuropathic pain, but it is still unknown how functional recovery is induced after peripheral nerve injury. We evaluated the effects of intranerve application of BoNT/A, on regeneration and sensorimotor functional recovery in partial and complete peripheral nerve injuries in the mouse. After sciatic nerve crush (SNC) and intranerve delivery of BoNT/A (15pg), axonal regeneration was measured by nerve pinch test at different days. Regeneration of myelinated and unmyelinated fibers was assessed by immunohistochemical double labeling for NF200/GAP43 and CGRP/GAP43. S100 was used as Schwann cells marker. Medial footpad skin reinnervation was assessed by PGP staining. Motor functions were assessed by means of nerve conduction tests. In other mice groups, nerve conduction tests were performed also after chronic constriction injury (CCI) of the sciatic nerve and intraplantar injection of BoNT/A (15pg). In SNC mice, BoNT/A increased the rate of axonal regeneration. The advantage of regrowing myelinated axons after BoNT/A injection was evidenced by longer NF200+ nerve profiles and confirmed by nerve histology. We observed also a higher expression of S100 in the distal portion of BoNT/A-injected regenerated nerves. In CCI mice, BoNT/A induced an increase in reinnervation of gastrocnemius and plantar muscles. These results show that a low dose of BoNT/A, insufficient to produce muscular dysfunction, conversely speeds up sensorimotor recovery by stimulating myelinated axonal regeneration, and points out its application as a multipotent treatment for peripheral neuropathies.
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