Deficiency of Endothelial Nitric Oxide Synthase (eNOS) Exacerbates Brain Damage and Cognitive Deficit in A Mouse Model of Vascular Dementia

• DOI: 10.14336/ad.2020.0523
• Publication Date: 2021-05-23T21:22:46Z
• Authors: Lulu An; Yi Shen; Michael Chopp; Alex Zacharek; Poornima Venkat; Zhili Chen; Wei Li; Yu Qian; Julie Landschoot-...; Jieli Chen
• Keywords: Vascular dementia; Neurological deficit

Vascular Dementia (VaD) accounts for nearly 20% of all cases dementia. eNOS plays an important role in neurovascular remodeling, anti-inflammation, and cognitive functional recovery after stroke. In this study, we investigated whether regulates brain damage, function mouse model bilateral common carotid artery stenosis (BCAS) induced VaD. Late-adult (6-8 months) C57BL/6J knockout (eNOS-/-) mice were subjected to BCAS (n=12/group) or sham group (n=8/group). was performed by applying microcoils both arteries. Cerebral blood flow (CBF) pressure measured. A battery tests performed, sacrificed 30 days BCAS. Compared corresponding mice, wild-type (WT) eNOS-/- significantly: 1) induces short term, long term memory loss, spatial learning deficits; 2) decreases CBF, increases ischemic cell including apoptosis, white matter (WM) axonal damage; 3) barrier (BBB) leakage, aquaporin-4 (AQP4) expression vessel density; 4) microglial, astrocyte activation oxidative stress the brain; 5) inflammatory factor interleukin-1 receptor-associated kinase-1(IRAK-1) amyloid beta (Aβ) 6) IL-6 IRAK4 brain. eNOS-/-sham exhibit increased pressure, decreased iNOS nNOS compared WT-sham mice. WT-BCAS eNOS-/-BCAS worse vascular WM/axonal BBB leakage response, deficit, iNOS, deficit exacerbates damage deficit.