CSF-1 promotes microglial proliferation and ameliorates ischemic brain injury.

Microglia play a pivotal role in the pathophysiology of ischemic stroke, with substantial microglial demise occurring following cerebral ischemia. This study examined whether colony-stimulating factor 1 (CSF-1) and interleukin-34 (IL-34), ligands of the colony-stimulating factor 1 receptor (CSF1R) critical for microglial survival, promote microglial proliferation and ameliorate outcomes after ischemic stroke. In a mouse model of middle cerebral artery occlusion (MCAO), endogenous CSF-1 levels showed dynamic changes within the first 24 h post-ischemia. Administration of CSF-1, but not IL-34, significantly improved neurological outcomes and reduced infarct volume. CSF-1 treatment was associated with a less reactive microglial morphology and an anti-inflammatory, homeostatic microglial phenotype. In vitro, CSF-1 enhanced Ki67 expression in oxygen-glucose deprivation (OGD)-exposed microglia, while decreasing pro-inflammatory cytokine production and excessive phagocytosis of neuronal debris. Conditioned medium from CSF-1-treated microglia and co-culture experiments further indicated that increased microglial numbers contribute to reduced OGD-induced neuronal apoptosis. Collectively, these findings suggest that CSF-1 fosters a neuroprotective microglial phenotype during acute ischemia, highlighting its potential as a therapeutic agent to mitigate ischemic brain injury through modulation of microglial proliferation and inflammatory responses.