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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • University of Caen Normandy
  • Skåne University Hospital
  • Centre Hospitalier Privé Saint-Martin
  • Lund University
  • Nencki Institute of Experimental Biology
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
  • Cell- och molekylärbiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)2196-2213
TidskriftMolecular Neurobiology
Volym55
Utgåva nummer3
Tidigt onlinedatum2017 mar 13
StatusPublished - 2018
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Miriana Quattromani, 2017, Lund: Lund University: Faculty of Medicine. 75 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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