Research Overview
Cerebral Circulation, Ischemic Brain Injury and Stroke
1. Cerebrovascular biology and regulation of the cerebral microcirculation in the normal state and in diseaseWe are interested in the mechanisms that regulate the cerebral circulation during neural activity and in the neurobiological basis of functional imaging signals. As a model of activation, we use stimulation of the whisker barrel cortex or activation of the cerebellar cortex by somatosensory or electrical stimuli. We employ genetically-engineered mice and pharmacological tools to study the role of specific gene products in this process. Ongoing research programs focus on the role of nitric oxide, and of cyclooxygenase-1 and 2 in normal cerebrovascular function and in disease states, such as arterial hypertension and Alzheimer#146;s disease. 2. Molecular pathology of cerebral ischemic injuryCerebral Ischemia produces a profound change in the pattern of gene expression in brain. Some genes are deleterious to the brain, while other genes are protective. We have active programs looking at the effect of inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and transcription factors including interferon regulatory factor 1 and nuclear factor-kb. We are pursuing molecular cascades leading to both necrosis and apoptosis. We are also studying the effects of cerebral ischemia on neurogenesis in the central nervous system, and the mechanisms of ischemic preconditioning, a therapeutically-important phenomenon by which a mild ischemic insult protects the brain from a subsequent more damaging insult. In these studies we use both in vivo and in vitro models of cerebral ischemia.For more information, please visit our website at:http://www.cornellneurology.org/neurobiology
