The Experimental Neurogenic Hypertension Program is a multidisciplinary research program investigating the neurobiology of central neural systems governing arterial pressure (AP), regulating the cerebral circulation, and protecting against cerebral ischemia. The broad objectives of this revised proposal are: (a) to investigate the organization within the rostral ventrolateral medulla (RVL) of neurons controlling regional cerebral blood flow (rCBF), and to characterize the efferent pathway, subcortical relay, and intracortical mechanisms by which electrical, chemical and hypoxic stimulation of the nucleus elevates rCBF; (b) to determine, by anatomical tracing methods, the anatomy of pathways by which visceral signals arising in the nucleus tractus solitarii (NST) ascend to influence the performance of thalamic and forebrain centers involved in processing emotional behaviors; to examine, using techniques of EM immunocytochemistry, the distribution and synaptic relationships of alpha2-2- adrenergic, mu and delta-opiate, and NMDA receptors in and around the perikarya and terminals of sympathoexcitatory reticulospinal neurons of RVL, particularly with respect to sites of action of clonidine; to establish, by similar methods, the sites of and interactions between these, and also the kappa-opioid receptors in NTS in relationship to vagal afferent fibers; (e) to analyze the cellular and genetic mechanisms by which electrical stimulation of the cerebellar fastigial nucleus (FN) can conditionally reduce the volume of focal ischemic infarctions of rat brain, either by modifying Kplus channels, and/or suppressing expression of pro-inflammatory genes, and/or facilitating expression of anti-inflammatory and neuroprotective genes.
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