Reactive astrocytes prevent maladaptive plasticity after ischemic stroke. (February 2022) - Aswendt, Markus
Graphical abstract: Highlights: Attenuation of reactive gliosis does not affect the acute loss of functional connectivity after ischemic stroke. In post-acute phase, attenuation of reactive gliosis leads to increased loss and gain of sensorimotor neuronal connections. Attenuation of reactive gliosis alters stroke-induced global neuronal connectivity responses and impairs functional recovery. 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.