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Timed microglia depletion promotes functional network reorganization and motor recovery after stroke
Sara Isla Cainzos1, Fanny Quandt1, Malte Borggrewe2
1Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
Abstract:
Pharmacological options to promote long-term rehabilitation after stroke remain limited. We investigated how short-term microglia depletion during the subacute phase after ischaemic stroke affects functional recovery and neuronal network dynamics. Using a C57BL/6 wild-type stroke model, fine motor performance was assessed with a skilled reaching task while bilateral cortical activity was recorded longitudinally through epidural electrocorticography. Microglia were depleted between days 3 and 7 post-stroke using PLX5622, a colony-stimulating factor 1 receptor inhibitor. Microglia depletion resulted in near-complete restoration of fine motor function by day 7 and was accompanied by significant functional connectivity changes in bilateral sensorimotor networks, including increased beta-band connectivity in the ipsilesional motor cortex, which correlated with contralateral fine motor improvement. Following repopulation, microglial cells showed altered morphology and gene expression profiles. These findings reveal that transient microglial modulation during the subacute phase after stroke promotes cortical network reorganization and motor recovery.
Insights
Transient microglia depletion during subacute stroke promotes motor recovery and brain network reorganization. This approach enhances functional connectivity, offering new avenues for stroke rehabilitation strategies.
Area of Science:
- Neuroscience
- Immunology
- Neurology
Background:
- Limited pharmacological options exist for long-term stroke rehabilitation.
- The role of microglia in post-stroke recovery is complex and requires further investigation.
Purpose of the Study:
- To investigate the effects of short-term microglia depletion during the subacute phase after ischemic stroke on functional recovery and neuronal network dynamics.
- To explore the potential of modulating microglia for enhancing motor function and brain network reorganization post-stroke.
Main Methods:
- Utilized a C57BL/6 wild-type mouse model of ischemic stroke.
- Administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, to deplete microglia between days 3 and 7 post-stroke.
- Assessed fine motor performance using a skilled reaching task and recorded bilateral cortical activity via epidural electrocorticography.
Main Results:
- Microglia depletion led to near-complete restoration of fine motor function by day 7 post-stroke.
- Observed significant functional connectivity changes in bilateral sensorimotor networks, including increased beta-band connectivity.
- Correlated increased ipsilesional motor cortex beta-band connectivity with contralateral fine motor improvement.
Conclusions:
- Transient microglial modulation during the subacute phase post-stroke promotes cortical network reorganization and motor recovery.
- Altered microglial morphology and gene expression were noted after repopulation, suggesting a lasting impact.
- These findings highlight microglia as a potential therapeutic target for improving stroke outcomes.
