Research Overview
This laboratory is directed by H. Richard Winn, M.D., Professor of Neurosurgery and Neuroscience and Director of Research for the Department of Neurosurgery. Dr. Winn has been continuously funded by the NIH since 1974 for this research.
The central focus of the laboratory is the regulation of cerebral blood flow (CBF) with particular emphasis on the adenine nucleoside, adenosine. We have shown that adenosine is a potent dilator of cerebral arterioles (J Cereb Blood Flow Metab 11:72-76, 1991; Circ Res 73:448-457, 1993; J Neurosci Methods 120:145-53, 2002). In the past, we have demonstrated that brain adenosine concentrations increase rapidly during ischemia and hypoxia and during seizures (Circ Res 45:486-492, 1979; Circ Res 47:568-577, 1980; Am J Physiol 241:H235-H242, 1981). Under the former conditions, oxygen delivery is decreased whereas in the latter state, demand for oxygen is increased. The trigger for adenosine production in the brain appears to be related to the balance between metabolism and supply of nutrients provided by CBF (J Cereb Blood Flow Metab 1:239-244, 1981. CBF is tightly tied to cerebral metabolism. In our present investigations, we utilize a variety of cellular and molecular techniques, including genetically engineered mice and in vitro and in vivo studies, in our effort to uncover the factors that control CBF (Am J Physiology Heart Circ. Physiol.280:H2329-35,2001; J Cardiovasc Pharmacol: 41:444-451, 2003; Am J Physiol Heart Circ Physiol. 284: H1631-H1637, 2003; Exp Neurol. 2003;183(1):188-96; J Cereb Blood Flow Metab, 2005;25(6):775-84). Further knowledge of mechanisms regulating CBF will provide a rational approach to the treatment of stroke and the impairment in CBF that occurs in head injuries.
Figure 1
Experimental Paradigm: The Role of Adenosine in the Regulation of CBF in Sensory Hindlimb Cortex during Sciatic Nerve Stimulation (SNS).
Figure 2
Video clip demonstrating brain arteriolar response to contra-lateral sciatic nerve stimulation.
Figure 3
Video clip demonstrating Optical imaging of sensory hindlimb cortex during sciatic nerve stimulation (Optical imaging at 550nm, sciatic nerve stimulation 20 sec, 0.2V, 5 Hz).
