Dr. Sean P. Marrelli
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Neurology
The first project explores multiple mechanisms by which TRPV1 channel activation can promote neuroprotection following stroke. These studies exploit the ability of capsaicinoids (TRPV1 agonists) to promote induced hypothermia by activating heat-sensitive neurons within the thermoregulatory system. We have employed TRPV1-mediated hypothermia in the post-stroke period to promote decreased primary brain injury as well as disruption of secondary injury. These studies also explore how endothelial TRPV1 channels contribute to blood flow during the reperfusion period.
The second project focuses on the role of endothelial von Willebrand Factor (VWF) strings in promoting post-stroke thrombosis. Following activation (such as by ischemia/reperfusion), cerebral endothelium releases stored VWF multimers into the vascular lumen. These multimers remain anchored to the endothelial surface and can form elongated strings. If these strings remain in the lumen, circulating platelets can bind, become activated, and contribute to thrombosis. We have recently targeted the attachment of these strings with a competitive protein, demonstrating both reduced string formation and improved cerebral reperfusion following stroke (Fasipe et al., Stroke 2018).
The third project seeks to improve neurorecovery from stroke through enhancing reparative angiogenesis in the brain. We are manipulating specific molecular pathways which regulate capillary sprouting to achieve enhanced recovery of perfusion-competent capillaries in brain regions adjacent to the infarct. An important component of these studies is the demonstration of improved functional outcome, particularly in aged mice.
My laboratory has specific expertise in intravital imaging, in vivo cerebral blood flow measurements (laser speckle contrast imaging, laser Doppler), confocal microscopy, measures of reparative angiogenesis, isolated pressurized arteries, patch clamp electrophysiology (K channels, TRP channels), intracellular calcium measurements, thermoregulation, therapeutic hypothermia, and general molecular techniques.