Ralph G. Dacey Jr, M.D.

DEPARTMENT OF Neurological Surgery
Keywords: CNS, microvasculature, regulation, imaging, drug testing

The work of this laboratory focuses on elucidating the mechanisms involved in cerebral microvascular regulation under normal and pathological conditions.

Endothelial cells and smooth muscle cells communicate in the walls of cerebral resistence arterioles to integrate the control of the cerebral microcirculation. Short-term hypoxia of as little as 10 minutes has been found to alter the physiological responses of larger arterial vessels, but cerebral microvessels have not been studied in detail. We want to elucidate the intracellular target for the hypoxic damage in either the endothelial or smooth muscle cell of cerebral arterioles and elucidate possible treatments to prevent such damage.

Technical approaches to examining these questions include: the use of voltage- and calcium-sensitive dyes with computer-aided video imaging, direct measurement of smooth muscle cell membrane potential, online vessel diameter measurements and use of pharmacological and molecular techniques to alter endothelial-smooth muscle function in small cerebral arterioles cannulated and perfused in vitro. Recent developments include the study of eNOS-deficient mice and cell culture of brain microvascular endothelial and smooth muscle cells.