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

Quattromani, Miriana Jlenia LU ; Pruvost, Mathilde; Guerreiro, Carla; Backlund, Fredrik; Englund, Elisabet LU ; Aspberg, Anders LU ; Jaworski, Tomasz; Christensen, Jakob Hakon LU ; Ruscher, Karsten LU and Kaczmarek, Leszek, et al. (2018) In Molecular Neurobiology 55(3). p.2196-2213
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... (More)

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.

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keywords
Experience-dependent plasticity, Extracellular matrix, Perineuronal nets, Proteases, Somatosensory cortex, Stroke recovery
in
Molecular Neurobiology
volume
55
issue
3
pages
2196 - 2213
publisher
Humana Press
external identifiers
  • scopus:85015004078
ISSN
0893-7648
DOI
10.1007/s12035-017-0461-2
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English
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yes
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ef532af8-d218-4166-9ec2-b39930c591ef
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2017-03-23 08:52:51
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2018-07-15 04:39:17
@article{ef532af8-d218-4166-9ec2-b39930c591ef,
  abstract     = {<p>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.</p>},
  author       = {Quattromani, Miriana Jlenia and Pruvost, Mathilde and Guerreiro, Carla and Backlund, Fredrik and Englund, Elisabet and Aspberg, Anders and Jaworski, Tomasz and Christensen, Jakob Hakon and Ruscher, Karsten and Kaczmarek, Leszek and Vivien, Denis and Wieloch, Tadeusz},
  issn         = {0893-7648},
  keyword      = {Experience-dependent plasticity,Extracellular matrix,Perineuronal nets,Proteases,Somatosensory cortex,Stroke recovery},
  language     = {eng},
  number       = {3},
  pages        = {2196--2213},
  publisher    = {Humana Press},
  series       = {Molecular Neurobiology},
  title        = {Extracellular Matrix Modulation Is Driven by Experience-Dependent Plasticity During Stroke Recovery},
  url          = {http://dx.doi.org/10.1007/s12035-017-0461-2},
  volume       = {55},
  year         = {2018},
}