EMMPRIN/CD147 Plays a Detrimental Role in Clinical and Experimental Ischemic Stroke

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Mar 20

PMID 32191628

Citations 17

Authors

Anthony Patrizz

Sarah J Doran

Anjali Chauhan

Hilda Ahnstedt

Meaghan Roy-OReilly

Yun-Ju Lai

Gillian Weston

Sami Tarabishy

Anita R Patel

Rajkumar Verma

Ilene Staff

Julia K Kofler

Jun Li

Fudong Liu

Rodney M Ritzel

Louise D McCullough

Affiliations

Soon will be listed here.

Abstract

Background: Ischemic stroke is a devastating disease, often resulting in death or permanent neurological deficits. EMMPRIN/CD147 is a plasma membrane protein that induces the production of matrix metalloproteinases (MMPs), which contribute to secondary damage after stroke by disrupting the blood brain barrier (BBB) and facilitating peripheral leukocyte infiltration into the brain.

Results: CD147 surface expression increased significantly after stroke on infiltrating leukocytes, astrocytes and endothelial cells, but not on resident microglia. Inhibition of CD147 reduced MMP levels, decreased ischemic damage, and improved functional, cognitive and histological outcomes after experimental ischemic stroke in both young and aged mice. In stroke patients, high levels of serum CD147 24 hours after stroke predicted poor functional outcome at 12 months. Brain CD147 levels were correlated with MMP-9 and secondary hemorrhage in post-mortem samples from stroke patients.

Conclusions: Acute inhibition of CD147 decreases levels of MMP-9, limits tissue loss, and improves long-term cognitive outcomes following experimental stroke in aged mice. High serum CD147 correlates with poor outcomes in stroke patients. This study identifies CD147 as a novel, clinically relevant target in ischemic stroke.

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