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.

Paulo W. Pires

Department of Pharmacology

University of Nevada School of Medicine

Isolation and Cannulation of Cerebral Parenchymal Arterioles

Isolation and Functional Analysis of Arteriolar Endothelium of Mouse Brain Parenchyma

Paulo W. Pires

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Pharmacology

University of Nevada School of Medicine

Isolation and Cannulation of Cerebral Parenchymal Arterioles

Isolation and Functional Analysis of Arteriolar Endothelium of Mouse Brain Parenchyma

Department of Pharmacology