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Open Access 01-04-2011 | Review

Role of Matrix Metalloproteinases and Therapeutic Benefits of Their Inhibition in Spinal Cord Injury

Authors: Haoqian Zhang, Mayland Chang, Christopher N. Hansen, D. Michele Basso, Linda J. Noble-Haeusslein

Published in: Neurotherapeutics | Issue 2/2011

Summary

This review will focus on matrix metalloproteinases (MMPs) and their inhibitors in the context of spinal cord injury (SCI). MMPs have a specific cellular and temporal pattern of expression in the injured spinal cord. Here we consider their diverse functions in the acutely injured cord and during wound healing. Excessive activity of MMPs, and in particular gelatinase B (MMP-9), in the acutely injured cord contributes to disruption of the blood-spinal cord barrier, and the influx of leukocytes into the injured cord, as well as apoptosis. MMP-9 and MMP-2 regulate inflammation and neuropathic pain after peripheral nerve injury and may contribute to SCI-induced pain. Early pharmacologic inhibition of MMPs or the gelatinases (MMP-2 and MMP-9) results in an improvement in long-term neurological recovery and is associated with reduced glial scarring and neuropathic pain. During wound healing, gelatinase A (MMP-2) plays a critical role in limiting the formation of an inhibitory glial scar, and mice that are genetically deficient in this protease showed impaired recovery. Together, these findings illustrate complex, temporally distinct roles of MMPs in SCIs. As early gelatinase activity is detrimental, there is an emerging interest in developing gelatinase-targeted therapeutics that would be specifically tailored to the acute injured spinal cord. Thus, we focus this review on the development of selective gelatinase inhibitors.

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Title: Role of Matrix Metalloproteinases and Therapeutic Benefits of Their Inhibition in Spinal Cord Injury
Authors: Haoqian Zhang
Mayland Chang
Christopher N. Hansen
D. Michele Basso
Linda J. Noble-Haeusslein
Publication date: 01-04-2011
Publisher: Springer-Verlag
Published in: Neurotherapeutics / Issue 2/2011
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI: https://doi.org/10.1007/s13311-011-0038-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Role of Matrix Metalloproteinases and Therapeutic Benefits of Their Inhibition in Spinal Cord Injury

Summary

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Summary

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