Selective Inhibition of MMP-2 Does Not Alter Neurological Recovery after Spinal Cord Injury

Ming Gao, Haoqian Zhang, Alpa Trivedi, Kiran V. Mahasenan, Valerie A. Schroeder, William R. Wolter, Mark A. Suckow, Shahriar Mobashery, Linda J. Noble-Haeusslein, Mayland Chang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Matrix metalloproteinase (MMP)-2 knockout (KO) mice show impaired neurological recovery after spinal cord injury (SCI), suggesting that this proteinase is critical to recovery processes. However, this finding in the KO has been confounded by a compensatory increase in MMP-9. We synthesized the thiirane mechanism-based inhibitor ND-378 and document that it is a potent (nanomolar) and selective slow-binding inhibitor of MMP-2 that does not inhibit the closely related MMP-9 and MMP-14. ND-378 crosses the blood-spinal cord barrier, achieving therapeutic concentrations in the injured spinal cord. Spinal-cord injured mice treated with ND-378 showed no change in long-term neurological outcomes, suggesting that MMP-2 is not a key determinant of locomotor recovery.

Original languageEnglish
Pages (from-to)1482-1487
Number of pages6
JournalACS Chemical Neuroscience
Volume7
Issue number11
DOIs
StatePublished - Nov 16 2016

Bibliographical note

Funding Information:
We thank Sandra Canchola and the Neurobehavioral Core for Rehabilitation Research at UCSF for providing the facilities to conduct the behavioral analyses.

Publisher Copyright:
© 2016 American Chemical Society.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • MMP-2
  • ND-378
  • brain distribution
  • spinal cord injury

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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