Early Blockade of Matrix Metalloproteinases in Spinal-Cord-Injured Dogs Results in a Long-Term Increase in Bladder Compliance

Journal of Neurotrauma
Jonathan M LevineLinda J Noble-Haeusslein

Abstract

Spinal cord injury (SCI) is often accompanied by reduced bladder compliance, which contributes to adverse conditions including urinary tract infections and vesicoureteral reflux. Reduced compliance is, in part, attributed to extensive remodeling of the bladder wall, including the extracellular matrix (ECM). Here, we tested the hypothesis that blockade of matrix metalloproteinases (MMPs), known for their ability to remodel the ECM, improves bladder compliance in dogs with SCI. We first evaluated dogs with naturally occurring SCIs resulting from intervertebral disc herniation (IVDH). After characterizing the natural history of urological recovery by cystometry in healthy dogs (n = 10) and dogs with SCIs (n = 20), we conducted a randomized, double-blinded, placebo-controlled clinical trial in dogs with IVDH-associated SCIs to assess the efficacy of the broad-spectrum MMP inhibitor, GM6001, given within 48 h post-injury. The primary outcomes were bladder compliance, as measured by cystometry, and an ordinal gait score (Texas Spinal Cord Injury Score; TSCIS) at day 42 post-SCI. Dogs (n = 93) were randomized to receive either dimethyl sulfoxide (DMSO) or GM6001+DMSO. There were transient, but significantly (p = 0.023) greater, advers...Continue Reading

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Citations

Sep 25, 2019·Topics in Spinal Cord Injury Rehabilitation·Laurie CookSarah Moore
Jan 10, 2020·Journal of Neurotrauma·Natasha OlbyUNKNOWN CANSORT SCI Investigators
Jun 7, 2019·Cellular and Molecular Life Sciences : CMLS·Alpa TrivediLinda L Phillips
Jun 6, 2019·Neurourology and Urodynamics·Fernanda C F S CalistoSalvador V C Lima
May 8, 2018·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Andrew D Gaudet, Laura K Fonken
Dec 3, 2020·Frontiers in Veterinary Science·Nicolas GrangerUNKNOWN Canine Spinal Cord Injury Consortium (CANSORT-SCI)
Nov 17, 2020·Frontiers in Veterinary Science·Melissa J LewisUNKNOWN Canine Spinal Cord Injury Consortium (CANSORT-SCI)

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
sedation

Software Mentioned

eFILM
PLUS

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