Docosahexaenoic acid protects against ischemic stroke in diabetic mice by inhibiting inflammatory responses and apoptosis

Abstract

This study was to explore whether docosahexaenoic acid (DHA) protects against ischemic stroke in diabetic mice and its mechanisms. DHA was administered to mice and its effects on stroke outcomes in type 1 diabetes mellitus were assessed 24 h and 3 days post-reperfusion using RNA sequencing, flow cytometry, multiplex immunoassays, and western-blotting analysis. In diabetic mice, DHA administration post-ischemic stroke significantly reduced cerebral infarct size, brain edema, and neurological impairments. Flow cytometric analysis demonstrated a notable decrease in the percentage of neutrophils in the ischemic brain, suggesting a mitigated inflammatory response. Western blotting assay revealed that pro-apoptotic protein Bax was reduced whereas anti-apoptotic protein Bcl-2 was increased, indicating the attenuation of apoptosis. Additionally, RNA sequencing of brain tissue highlighted significant transcriptomic changes, with downregulation of genes for several inflammatory pathways such as NF-kappa B signaling and upregulation of genes for neuroprotective pathways such as neuroactive ligand-receptor interaction. Similar transcriptomic changes in peripheral blood mononuclear cells indicated that DHA treatment resulted the systemic anti-inflammatory and neuroprotective response. DHA treatment mitigated cerebral ischemic injuries by dampening inflammatory responses and apoptosis in diabetic mice after ischemic stroke, highlighting its therapeutic potential for clinical management of stroke in diabetic patients.