Abstract TMP116: Gut-derived extracellular vesicles promote neurovascular damage and cognitive impairment in diabetic mice

• DOI: 10.1161/str.56.suppl_1.tmp116
• Publication Date: 2025-01-30T10:27:49Z
• Authors: Xianshuang Liu; Michael Chopp; Baoyan Fan; Xinli Wang; Xu Cui; Brianna Powell; Mikkala Mccann; Julie Landschoot-...; Zheng Gang Zhang
• Keywords: Neurovascular bundle; Extracellular Vesicles; Stroke

Background and Purpose: Gut microbiota dysfunction is associated with diabetic cognitive impairment (DCI). However, the mechanisms underlying interaction of gut dysbiosis DCI remain poorly understood. We tested hypothesis that extracellular vesicles generated by exacerbate promoting cerebral vascular function. Methods: Gut-EVs from stools male non-diabetic dm (dm-gut-EVs) (db/db mice) (db-gut-EVs) mice at 20 weeks age (20W) were isolated characterized means ultracentrifugation 16S rRNA sequencing, respectively. Given db/db develop deficits 20W, prediabetic 8 (8W) treated gut-EVs a dose 1x10 10 particles/injection intravenously twice week for 12 weeks. Cognitive performance was assessed using battery behavioral tests. Results: analysis revealed significant alterations in composition db-gut-EVs derived 20W compared to dm-gut-EVs (n=5/group). Db/db extracted but not dm-gut-EVs, exhibited decline learning memory function, as assayed Novel object recognition, Social recognition memory, Morris water maze assay, starting 16W worsening saline (n=10/group). Additionally, increased thrombosis (18±2 vs 11±2 Fibrin+ vessels/mm 2 saline, p<0.05, n=5/group), whereas showed reduction (5±0.5 , p<0.05). In vitro, treatment human endothelial cells (hCECs) significantly (p<0.05) upregulated pro-coagulation inflammatory proteins, including plasminogen activator inhibitor-1 (PAI-1), tissue factor (TF), NF-κB, intercellular adhesion molecule 1 (ICAM-1), while reducing tight junction protein ZO-1 expression. Conclusions: Our findings indicate promote inducing damage, underscore major role microbiota-brain communication development DCI.