Abstract 146: Transient Receptor Potential Vanilloid 1 (TRPV1) Channel Contributes to Cerebral Reperfusion after Stroke
Stroke(2017)
摘要
Introduction: The TRPV1 channel is a non-selective ion channel that is activated by capsaicinoids, temperature (u003e43 °C), and multiple factors produced during inflammation or injury. At this time, there is very little reported regarding a role of this channel in regulation of cerebral blood flow. Here we provide new evidence for TRPV1 in promoting microvascular reperfusion following stroke. Hypothesis: Endothelial TRPV1 channels contribute to cerebral reperfusion following ischemic stroke. Methods: Experiments were performed in male WT and TRPV1 knockout mice of C57BL/6 background. Immunofluorescence was performed in brain sections with TRPV1 and Pecam-1 antibodies. Pressurized artery preparations were performed with isolated superior cerebellar arteries. Relative cerebral blood flow measurements were performed by laser Doppler and laser speckle flowmetry in mice before, during, and after MCAO (20 or 30 min). Reperfusion was monitored continuously for 2-3 hours and again at 24 hours. Results: TRPV1 expression was positively detected by immunofluorescence in the cerebral microvasculature, as assessed by Pecam-1 co-localization. TRPV1 KO mice were used as a negative control. Pressurized cerebral arteries demonstrated modest vasodilation to TRPV1 agonist (capsaicin) that was significantly potentiated with H 2 O 2 pre-treatment. The potentiated component of vasodilation was lost with removal of the endothelium, demonstrating the endothelial source of the response. Following brief MCA occlusion (20 or 30 min), WT mice demonstrated an initial return of cerebral perfusion followed by a transient drop in perfusion (~25% drop). This drop in perfusion started at 20-30 minutes into the reperfusion phase and lasted approximately one hour, at which point perfusion was restored to pre-stroke baseline value. In TRPV1 KO mice, the drop in perfusion was more profound (~65% drop) and persisted through 3 hours. By 24 hours, flow was restored to baseline in both groups. Conclusions: These data demonstrate a functional role for TRPV1 channels during reperfusion. We speculate that endothelial TRPV1 channels are functionally potentiated during injury and contribute to the vasodilatory capacity of the cerebral microvasculature following stroke.
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