New paper 🔊.Our team under Prof S T Dheen & @JaiPolepalli in collaboration with @garriearumugam uncovers how HDACi reprograms microglia in the stroke brain using spatial transcriptomics. 🧠 🧬 #Neuroinflammation #Stroke #Epigenetics #Glia #10XGenomics

8/ 💡 Take-home message:.Epigenetic modulation via HDACi reprograms microglial function & spatiotranscriptomes in stroke;.Exhibits potential for cell-centric, spatially targeted therapies in neurovascular diseases.Full study: #neuroscience #HDACi #stroke.

7/ 🧬 Astrocytes and neurons also showed regional transcriptional rescue via HDACi, including lipid metabolism, junctional signaling & neurotrophic support. #Astrocytes #Neurons #Spatiotranscriptomics.

6/ 🔎 Microglial phenotypic rescue was confirmed:. Microglia regained ramified morphologies. FcγRI (CD64) and PI3K protein expression levels were normalized. Microglial soma and process morphometrics affirmed reversal of ischemic changes.

5/ 🧠 Epigenetic Regulation.HDACi modulated microglial expression of:. H3K27me3 .&.H3K4me3 . This potentially reshaped microglial transcriptomes toward the observed neuroprotective and anti-inflammatory profiles in the key regions of interest within the stroke brain.

4/ 🔬 Spatial transcriptomics (10X Visium) revealed that HDACi rescues microglial gene signatures with unique heterogeneity across regions (i.e. hippocampus, cortex, striatum, thalamus). 🧬 Key targets & signalling pathways rescued:. PI3K-Akt. MAPK. TNF/TGF. FcγR Phagocytosis.

3/ 🧪 Using the MCAo model of ischemic stroke in mice, we administered the HDAC inhibitor sodium butyrate at previously established dosages. Our goal: Rewire microglial response and assess it at key brain regions to identify unique spatial signatures.

2/ 🧠 Why microglia?.These brain-resident immune cells are first responders in stroke, but their activation can either protect or worsen damage. We studied how epigenetic modulation shapes this duality in the ischemic penumbra. #microglia #stroke.