title: Extracellular Matrix Modulation Is Driven by Experience-Dependent Plasticity During Stroke Recovery.
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.
authors.affiliation: Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, 22184, Lund, Sweden. miriana.quattromani@med.lu.se.
authors.forename: Miriana Jlenia
authors.initials: MJ
authors.lastname: Quattromani
authors.affiliation: INSERM UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse Normandie, GIP Cyceron, F-14074, Caen, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Pruvost
authors.affiliation: Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, 22184, Lund, Sweden.
authors.forename: Carla
authors.initials: C
authors.lastname: Guerreiro
authors.affiliation: Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, 22184, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Backlund
authors.affiliation: Division of Oncology and Pathology, Lund University Hospital, 22185, Lund, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Englund
authors.affiliation: Rheumatology and Molecular Skeletal Biology, Department of Clinical Sciences, Lund University, BMC C12, 22184, Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Aspberg
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jaworski
authors.affiliation: Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, 22184, Lund, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Hakon
authors.affiliation: Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, 22184, Lund, Sweden.
authors.forename: Karsten
authors.initials: K
authors.lastname: Ruscher
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.affiliation: INSERM UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse Normandie, GIP Cyceron, F-14074, Caen, France.|Department of Clinical Research, Caen University Hospital, CHU Caen, 14000, Caen, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, 22184, Lund, Sweden.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Wieloch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004777:Environment; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000378:metabolism* / Q000473:pathology; D000071939:Stroke Rehabilitation / Q000379:methods* / Q000639:trends
chemical_list: D018836:Inflammation Mediators
keywords: Experience-dependent plasticity; Extracellular matrix; Perineuronal nets; Proteases; Somatosensory cortex; Stroke recovery