Extracellular Matrix Modulation Is Driven by Experience-Dependent Plasticity During Stroke Recovery

Research output: Contribution to journalArticle

Abstract

Following stroke, complete cellular death in the ischemic brain area may ensue, with remaining brain areas undergoing tissue remodelling to various degrees. Experience-dependent brain plasticity exerted through an enriched environment (EE) promotes remodelling after central nervous system injury, such as stroke. Post-stroke tissue reorganization is modulated by growth inhibitory molecules differentially expressed within the ischemic hemisphere, like chondroitin sulfate proteoglycans found in perineuronal nets (PNNs). PNNs in the neocortex predominantly enwrap parvalbumin-containing GABAergic (PV/GABA) neurons, important in sensori-information processing. Here, we investigate how extracellular matrix (ECM) proteases and their inhibitors may participate in the regulation of PNN integrity during stroke recovery. Rats were subjected to photothrombotic stroke in the motor cortex, and functional deficits were assessed at 7 days of recovery. Sham and stroked rats were housed in either standard or EE conditions for 5 days, and infarct volumes were calculated. PNNs were visualized by immunohistochemistry and counted in the somatosensory cortex of both hemispheres. mRNA expression levels of ECM proteases and protease inhibitors were assessed by RT-qPCR and their activity analyzed by gel zymography. PNNs and protease activity were also studied in brains from stroke patients where similar results were observed. EE starting 2 days after stroke and continuing for 5 days stimulated behavioral recovery of limb-placement ability without affecting infarct size. EE promoted a decrease of PNNs around PV/GABA neurons and a concomitant modulation of the proteolytic activity and mRNA expression of ECM proteases and protease inhibitors in the somatosensory cortex. This study provides molecular targets for novel therapies that could support rehabilitation of stroke patients.

Details

Authors
Organisations
External organisations
  • University of Caen Normandy
  • Skåne University Hospital
  • Centre Hospitalier Privé Saint-Martin
  • Lund University
  • Nencki Institute of Experimental Biology of of the Polish Academy of Sciences
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
  • Cell and Molecular Biology

Keywords

  • Experience-dependent plasticity, Extracellular matrix, Perineuronal nets, Proteases, Somatosensory cortex, Stroke recovery
Original languageEnglish
Pages (from-to)2196-2213
JournalMolecular Neurobiology
Volume55
Issue number3
Early online date2017 Mar 13
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes

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