Targeting microglial PPARa ameliorates the outcome of ischaemic stroke by enhancing interaction with infiltrating peripheral monocytes/macrophages

Microglial PPARa downregulation enhances inflammation and worsens ischemic brain injury by promoting Mo/MF infiltration, shifting them to a proinflammatory state, and disrupting the BBB. Restoring PPARa expression via AAV transfection reverses these effects, exerting neuroprotection by enhancing microglia–macrophage crosstalk through IL-4 signaling. Targeting microglial PPARa may offer a therapeutic strategy for mitigating acute ischemic stroke. Overall design: Primary microglia were isolated from CD45.2 WT and KO mice and subjected to OGD followed by reoxygenation. During reoxygenation, peritoneal macrophages from CD45.1 mice were introduced for co-culture. After a defined period, CD45.1? microglia were sorted and subjected to RNA-seq.