Reactive astrocytes prevent maladaptive plasticity after ischemic stroke

Markus Aswendt; Ulrika Wilhelmsson; Frederique Wieters; Anna Stokowska; Felix Johannes Schmitt; Niklas Pallast; Yolanda de Pablo; Lava Mohammed; Mathias Hoehn; Marcela Pekna; Milos Pekny

doi:10.1016/j.pneurobio.2021.102199

Reactive astrocytes prevent maladaptive plasticity after ischemic stroke

Prog Neurobiol. 2022 Feb:209:102199. doi: 10.1016/j.pneurobio.2021.102199. Epub 2021 Dec 15.

Affiliations

¹ University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany. Electronic address: [email protected].
² Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
³ University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany.
⁴ Laboratory of Regenerative Neuroimmunology, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁵ Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Juelich, Juelich, Germany.
⁶ Laboratory of Regenerative Neuroimmunology, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: [email protected].
⁷ Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; University of Newcastle, Newcastle, NSW, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. Electronic address: [email protected].

PMID: 34921928
DOI: 10.1016/j.pneurobio.2021.102199

Abstract

Restoration of functional connectivity is a major contributor to functional recovery after stroke. We investigated the role of reactive astrocytes in functional connectivity and recovery after photothrombotic stroke in mice with attenuated reactive gliosis (GFAP^-/-Vim^-/-). Infarct volume and longitudinal functional connectivity changes were determined by in vivo T2-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Sensorimotor function was assessed with behavioral tests, and glial and neural plasticity responses were quantified in the peri-infarct region. Four weeks after stroke, GFAP^-/-Vim^-/- mice showed impaired recovery of sensorimotor function and aberrant restoration of global neuronal connectivity. These mice also exhibited maladaptive plasticity responses, shown by higher number of lost and newly formed functional connections between primary and secondary targets of cortical stroke regions and increased peri-infarct expression of the axonal plasticity marker Gap43. We conclude that reactive astrocytes modulate recovery-promoting plasticity responses after ischemic stroke.

Keywords: Functional connectivity; Intermediate filaments (nanofilaments); MRI; Reactive gliosis; Recovery; Stroke.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / metabolism
Gliosis / metabolism
Humans
Ischemic Stroke*
Mice
Neuronal Plasticity
Recovery of Function / physiology
Stroke*