Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery post stroke.
Extracellular matrix
Fluorescence nanoscopy
Neuroinflammation
Parvalbumin interneurons
Stroke recovery
Synaptic rewiring
Journal
Journal of biomedical science
ISSN: 1423-0127
Titre abrégé: J Biomed Sci
Pays: England
ID NLM: 9421567
Informations de publication
Date de publication:
01 Sep 2023
01 Sep 2023
Historique:
received:
06
03
2023
accepted:
29
08
2023
medline:
4
9
2023
pubmed:
2
9
2023
entrez:
1
9
2023
Statut:
epublish
Résumé
Stroke remains one of the leading causes of long-term disability worldwide, and the development of effective restorative therapies is hindered by an incomplete understanding of intrinsic brain recovery mechanisms. Growing evidence indicates that the brain extracellular matrix (ECM) has major implications for neuroplasticity. Here we explored how perineuronal nets (PNNs), the facet-like ECM layers surrounding fast-spiking interneurons, contribute to neurological recovery after focal cerebral ischemia in mice with and without induced stroke tolerance. We investigated the structural remodeling of PNNs after stroke using 3D superresolution stimulated emission depletion (STED) and structured illumination (SR-SIM) microscopy. Superresolution imaging allowed for the precise reconstruction of PNN morphology using graphs, which are mathematical constructs designed for topological analysis. Focal cerebral ischemia was induced by transient occlusion of the middle cerebral artery (tMCAO). PNN-associated synapses and contacts with microglia/macrophages were quantified using high-resolution confocal microscopy. PNNs undergo transient structural changes after stroke allowing for the dynamic reorganization of GABAergic input to motor cortical L5 interneurons. The coherent remodeling of PNNs and their perforating inhibitory synapses precedes the recovery of motor coordination after stroke and depends on the severity of the ischemic injury. Morphological alterations in PNNs correlate with the increased surface of contact between activated microglia/macrophages and PNN-coated neurons. Our data indicate a novel mechanism of post stroke neuroplasticity involving the tripartite interaction between PNNs, synapses, and microglia/macrophages. We propose that prolonging PNN loosening during the post-acute period can extend the opening neuroplasticity window into the chronic stroke phase.
Sections du résumé
BACKGROUND
BACKGROUND
Stroke remains one of the leading causes of long-term disability worldwide, and the development of effective restorative therapies is hindered by an incomplete understanding of intrinsic brain recovery mechanisms. Growing evidence indicates that the brain extracellular matrix (ECM) has major implications for neuroplasticity. Here we explored how perineuronal nets (PNNs), the facet-like ECM layers surrounding fast-spiking interneurons, contribute to neurological recovery after focal cerebral ischemia in mice with and without induced stroke tolerance.
METHODS
METHODS
We investigated the structural remodeling of PNNs after stroke using 3D superresolution stimulated emission depletion (STED) and structured illumination (SR-SIM) microscopy. Superresolution imaging allowed for the precise reconstruction of PNN morphology using graphs, which are mathematical constructs designed for topological analysis. Focal cerebral ischemia was induced by transient occlusion of the middle cerebral artery (tMCAO). PNN-associated synapses and contacts with microglia/macrophages were quantified using high-resolution confocal microscopy.
RESULTS
RESULTS
PNNs undergo transient structural changes after stroke allowing for the dynamic reorganization of GABAergic input to motor cortical L5 interneurons. The coherent remodeling of PNNs and their perforating inhibitory synapses precedes the recovery of motor coordination after stroke and depends on the severity of the ischemic injury. Morphological alterations in PNNs correlate with the increased surface of contact between activated microglia/macrophages and PNN-coated neurons.
CONCLUSIONS
CONCLUSIONS
Our data indicate a novel mechanism of post stroke neuroplasticity involving the tripartite interaction between PNNs, synapses, and microglia/macrophages. We propose that prolonging PNN loosening during the post-acute period can extend the opening neuroplasticity window into the chronic stroke phase.
Identifiants
pubmed: 37658339
doi: 10.1186/s12929-023-00971-x
pii: 10.1186/s12929-023-00971-x
pmc: PMC10474719
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
76Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 467228103
Organisme : Deutsche Forschungsgemeinschaft
ID : 389030878
Organisme : Deutsche Forschungsgemeinschaft
ID : 405358801
Organisme : Deutsche Forschungsgemeinschaft
ID : 428817542
Organisme : Deutsche Forschungsgemeinschaft
ID : 449437943
Organisme : Deutsche Forschungsgemeinschaft
ID : 514990328
Informations de copyright
© 2023. National Science Council of the Republic of China (Taiwan).
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