Minocycline promotes functional recovery in ischemic stroke by modulating microglia polarization through STAT1/STAT6 pathways

Increasing evidence suggests that microglia experience two distinct phenotypes after acute ischemic stroke (AIS): a deleterious M1 phenotype and neuroprotective M2 phenotype. Promoting the shift of to is thought improve functional recovery AIS. Minocycline, tetracycline antibiotic, can cerebral ischemia in pre-clinical clinical research. However, role mechanisms minocycline polarization unclear. Using transient middle artery occlusion - reperfusion (MCAO/R) model, we treated mice with saline or different concentration (10, 25, 50 mg/kg, i.p., daily for 2 wk) at 24 h reperfusion. Neurobehavioral evaluation, rotarod test, corner turning test were carried out on day 14 Then, neuronal injury, reactive gliosis, performed 7 following MCAO/R. Finally, primary microglial cultures LPS (Lipopolysaccharide; 100 ng/mL) plus IFN-? (20 induce observed effects M1/M2-related mRNAs STAT1/STAT6 pathway. We found 14-day treatment increased survival rate promoted outcomes evaluated neurobehavioral test. Meanwhile, reduced brain infarct volume, alleviated suppressed gliosis Moreover, an additive effect vivo vitro. In microglia, further prevented neurons from OGD/R-induced cell death neuron-microglia co-cultures via regulating M1/M2 through Minocycline inhibited polarization, leading neurological recovery. The findings deepen our understanding underlying minocycline-mediated neuroprotection