Characterisation of matrix metalloproteinases and the effects of a broad-spectrum inhibitor (BB-1101) in peripheral nerve regeneration

The effect of treatment with a broad-spectrum inhibitor (BB1101) of the matrix metalloproteinases (MMPs) on nerve regeneration and functional recovery after nerve crush was examined. Drug treatment had no effect on latency but from 63 days the compound muscle action potential was significantly incre...

Full description

Saved in:

Bibliographic Details
Published in:	Neuroscience Vol. 124; no. 4; pp. 767 - 779
Main Authors:	Demestre, M, Wells, G.M, Miller, K.M, Smith, K.J, Hughes, R.A.C, Gearing, A.J, Gregson, N.A
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 2004 Elsevier
Subjects:	Action Potentials Animals Axons - pathology Benzyl Compounds Biological and medical sciences Dexamethasone - pharmacology Drug Combinations Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Immunohistochemistry Male Matrix Metalloproteinases - genetics Matrix Metalloproteinases - metabolism MMP-2 MMP-3 MMP-9 Muscle Fibers, Skeletal - pathology Muscles - physiopathology Myelin Sheath - pathology Nerve Crush Nerve Degeneration - physiopathology Nerve Regeneration - drug effects Neural Conduction - drug effects Pentoxifylline - pharmacology Peptide Hydrolases - metabolism Protein Isoforms - genetics Protein Isoforms - metabolism proteinases Rats Rats, Inbred Lew Recovery of Function reinnervation RNA, Messenger - metabolism Sciatic Nerve - physiopathology Succinates Tissue Distribution Vertebrates: nervous system and sense organs Wallerian degeneration PBS JOE Wallerian degeneration CMAP NMJ NGF TNF ECM MMP FITC MT1-MMP EAN FAM MMP-2 proteinases RT-PCR MMP-3 GAP reinnervation MMP-9 GAPDH Peripheral nerve Enzyme Metalloendopeptidases Gelatinase B Gelatinase A Peptidases Regeneration Hydrolases Reinnervation
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The effect of treatment with a broad-spectrum inhibitor (BB1101) of the matrix metalloproteinases (MMPs) on nerve regeneration and functional recovery after nerve crush was examined. Drug treatment had no effect on latency but from 63 days the compound muscle action potential was significantly increased and was no different to that in the sham-operated controls at 72 days. Levels of MMP mRNA expression, and the localisation and activity of MMP proteins, were examined in rats for a 2 month period following a nerve crush injury, and compared with sham-operated controls. The mRNA of all the MMPs studied was up-regulated by 5–10 days after nerve crush, and they remained up-regulated for 40–63 days, except for MMP-9 which was down-regulated by 10 days. MMP immunoreactivity was localised to Schwann cells, macrophages and endothelial cells, and with the exception of membrane type 1-MMP (MT1-MMP), it was more intense after nerve crush compared with sham-operated controls. Regenerating axons showed immunoreactivity for MMP-2 and MMP-3. In situ zymography confirmed that the activity of MMPs in the nerve was increased following crush but that the activity was greatly reduced in rats treated with BB-1101. Thus despite the inhibition of MMPs by BB-1101, the drug did not appear to essentially affect nerve degeneration or regeneration following nerve crush but that it could be beneficial in promoting the more effective reinnervation of muscles possibly by actions at the level of the muscles.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2003.12.037