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

• Published in: Molecular neurobiology Vol. 55; no. 3; pp. 2196 - 2213
• Main Authors: Quattromani, Miriana Jlenia, Pruvost, Mathilde, Guerreiro, Carla, Backlund, Fredrik, Englund, Elisabet, Aspberg, Anders, Jaworski, Tomasz, Hakon, Jakob, Ruscher, Karsten, Kaczmarek, Leszek, Vivien, Denis, Wieloch, Tadeusz
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2018; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Animals; Basic Medicine; Behavioral plasticity; Biomedical and Life Sciences; Biomedicine; Brain; Cell and Molecular Biology; Cell Biology; Cell- och molekylärbiologi; Central nervous system; Chondroitin sulfate; Cortex (motor); Enrichment; Environment; Experience-dependent plasticity; Extracellular matrix; Extracellular Matrix - metabolism; Female; Gene expression; Humans; Immunohistochemistry; Inflammation Mediators - metabolism; Information processing; Ischemia; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; Neurobiology; Neurology; Neuronal Plasticity - physiology; Neurosciences; Neurovetenskaper; Parvalbumin; Perineuronal nets; Plasticity; Proteases; Proteinase inhibitors; Proteoglycans; Proteolysis; Rats; Recovery of Function - physiology; Rehabilitation; Rodents; Somatosensory cortex; Stroke; Stroke - metabolism; Stroke - pathology; Stroke recovery; Stroke Rehabilitation - methods; Stroke Rehabilitation - trends; Sulfates; γ-Aminobutyric acid; Somatosensory cortex; Extracellular matrix; Stroke recovery; Experience-dependent plasticity; Perineuronal nets; Proteases
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-017-0461-2

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.