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Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery post stroke.

Authors
  • Dzyubenko, Egor1
  • Willig, Katrin I2
  • Yin, Dongpei3
  • Sardari, Maryam3
  • Tokmak, Erdin3
  • Labus, Patrick3
  • Schmermund, Ben3
  • Hermann, Dirk M4
  • 1 Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. [email protected]. , (Germany)
  • 2 Group of Optical Nanoscopy in Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Hermann-Rein-Str. 3, 37075, Göttingen, Germany. , (Germany)
  • 3 Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. , (Germany)
  • 4 Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. [email protected]. , (Germany)
Type
Published Article
Journal
Journal of Biomedical Science
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Sep 01, 2023
Volume
30
Issue
1
Pages
76–76
Identifiers
DOI: 10.1186/s12929-023-00971-x
PMID: 37658339
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © 2023. National Science Council of the Republic of China (Taiwan).

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