Research Paper Volume 12, Issue 6 pp 5121—5139

EMMPRIN/CD147 plays a detrimental role in clinical and experimental ischemic stroke

Anthony Patrizz 1, , Sarah J. Doran 2, , Anjali Chauhan 1, , Hilda Ahnstedt 1, , Meaghan Roy-O’Reilly 1, , Yun-Ju Lai 1, , Gillian Weston 2, , Sami Tarabishy 2, , Anita R. Patel 2, 3, , Rajkumar Verma 3, , Ilene Staff 3, , Julia K. Kofler 5, , Jun Li 1, , Fudong Liu 1, , Rodney M. Ritzel 4, , Louise D. McCullough 1, ,

  • 1 The University of Texas Health Science Center at Houston and the McGovern Medical School, Houston, TX 77030, USA
  • 2 Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA
  • 3 The Stroke Center at Hartford Hospital, Hartford, CT 06102, USA
  • 4 Department of Anesthesiology, Center for Shock, Trauma, and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA
  • 5 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA

received: September 18, 2019 ; accepted: January 27, 2020 ; published: March 19, 2020 ;

https://doi.org/10.18632/aging.102935
How to Cite

Copyright © 2020 Patrizz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

EMMPRIN/CD147: Extracellular Matrix Metallo proteinase Inducer; MMP: Matrix Metalloproteinase; BBB: Blood Brain Barrier; MCAO: Middle cerebral artery occlusion; ST: Stroke surgery; SH: Sham surgery; AIS: Acute ischemic stroke; ICH: Hemorrhagic stroke.