Spatio-Transcriptomic Analysis Reveals HDAC inhibition Modulates Microglial Dynamics to Protect Against Ischemic Stroke in Mice

Ischemic stroke is a leading cause of long-term disability worldwide, resulting from the occlusion of cerebral arteries that lead to extensive neuronal damage and inflammation. Microglia, resident immune cells of the brain, play a dual role in exacerbating and ameliorating post-stroke pathology. Despite growing evidence of their importance, the therapeutic potential of modulating microglial activity, particularly through epigenetic mechanisms, remains underexplored.Our research investigates the therapeutic potential of sodium butyrate, a histone deacetylase inhibitor (HDACi) to modulate microglial dynamics post-ischemic stroke. Using the surgical mouse model of middle cerebral artery occlusion (MCAo) and cutting-edge techniques such as spatial transcriptomics alongside microscopy based morphometric reconstruction, we analysed microglial responses in pertinent brain regions. Our findings suggest HDACi modulates microglial response after stroke to promote an environment conducive to neuronal recovery.