Abstract TMP119: Suppression of microRNA-145 alleviates the vascular cognitive impairment in a multiple microinfarction model

• DOI: 10.1161/str.56.suppl_1.tmp119
• Publication Date: 2025-01-30T10:27:49Z
• Authors: Huanjia Gao; Alex Zacharek; Brianna Powell; Mikkala Mccann; Zhenggang Zhang; Michael Chopp; Xianshuang Liu
• Keywords: Vascular dementia; Stroke

Background: Vascular cognitive impairment (VCI) is the second most frequent subtype of dementia following Alzheimer's disease. However, underlying mechanism has not been fully understood and there no effective treatment for VCI. MicroRNAs (miRNAs) play critical roles in pathologies cerebral ischemia dementia. This study aims to identify key miRNAs that may mediate outcomes using multiple microinfarction (MMI), a VCI model. Methods: MMI was induced by administration cholesterol crystals (70-100µm) into internal carotid artery. Male Wistar rats (10-12 month) subjected or sham operation were euthanized 28 days after (n=8/group). Total RNAs isolated from striatal tissues miRNA-sequencing performed. AAV-PHP.Eb carrying miR-145-5p sponge delivered Intracerebroventricular injection at 2 prior knockdown miR-145-5p. The mNSS (modified Neurological Severity Score) cognition tests examined weeks MMI. Results: MiRNA-sequencing analysis showed compared rats, significantly up- down-regulated 4 9 respectively. Bioinformatics revealed these highly associated with oligodendrocytes/myelination (miR-210 miR-125), BBB (miR-665 miR-29), inflammation (miR-322), etc. Amongst them, miR-145 top upregulated miRNA striatum In situ hybridization demonstrated expression smooth muscle cells, which negatively correlated decrease contraction marker cells (SMCs). Treatment AAV-miR-145 reduced sensorimotor deficits assayed lower score. Furthermore, administered spent less time on closed arm EPM (AAV-miR-145 VS control AAV: 182±28 263±9 (s), P=0.01) freezing OFT 205±9 246±11 P=0.015), those treated AAV. These data indicate inhibition reduces depression-like behavior deficit Conclusion: Our results uncovered deregulated myelination, white matter vascular damage Also, our suggest could be potential therapeutic target regulation SMCs against Thus, provides new insights molecular mechanisms