isolation-and-cannulation-of-cerebral-parenchymal-arterioles

Isolation and Cannulation of Cerebral Parenchymal Arterioles

Intracerebral parenchymal arterioles (PAs), which include parenchymal arterioles, penetrating arterioles and pre-capillary arterioles, are high resistance ...

isolation-functional-analysis-arteriolar-endothelium-mouse-brain

Isolation and Functional Analysis of Arteriolar Endothelium of Mouse Brain Parenchyma

Cerebral blood flow is conveyed by vascular resistance arteries and downstream parenchymal arterioles. Steady-state vascular resistance to blood flow ...

University of Nevada School of Medicine

University of Arizona College of Medicine Tucson

Transient increases in intracellular Ca activate endothelium-dependent vasodilatory pathways. This process is impaired in cerebral amyloid angiopathy, where amyloid- accumulates around blood vessels. In neurons, amyloid- impairs the Ca-permeable N-methyl-D-aspartate receptor (NMDAR), a mediator of endothelium-dependent dilation in arteries. We hypothesized that amyloid- reduces NMDAR-elicited Ca signals in mouse cerebral artery endothelial cells, blunting dilation. Cerebral arteries isolated from 4-5 months-old, male and female  mice were used for imaging of unitary Ca influx through NMDAR () and intracellular Ca transients. The NMDAR agonist NMDA (10 µmol/L) increased frequency of  and intracellular Ca transients in endothelial cells; these effects were prevented by NMDAR antagonists D-AP5 and MK-801. Next, we tested if amyloid- impairs NMDAR-elicited Ca transients. Cerebral arteries incubated with amyloid- (5 µmol/L) exhibited reduced  and intracellular Ca transients. Lastly, we observed that NMDA-induced dilation of pial arteries is reduced by acute intraluminal amyloid-, as well as in a mouse model of Alzheimer's disease, the , linked to downregulation of  mRNA compared to wild-type littermates. These data suggest that endothelial NMDAR mediate dilation via Ca-dependent pathways, a process disrupted by amyloid- and impaired in  mice.

ArticleTotal : 2	Year
Publication title Cited by 28	2016
Publication title Cited by 2	2022

Paulo W. Pires

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