Regulation of CBF by the Rostral Ventrolateral Medulla

描述（由申请方提供）：本研究的长期目标是确定大脑调节自身血流的神经元通路以及细胞成分和功能。它假定存在一个专用的脑血管扩张剂网络，它可以提高局部脑血流量（rCBF）的全球没有平行的变化，局部代谢（局部脑葡萄糖利用，rCGU）作为一个主要的血管扩张。该通路（a）与延髓头端腹外侧（RVLM）的脑干中心密切相关，该脑干中心感知并启动rCBF升高以响应缺氧;（B）通过延髓的相邻区域（延髓腹外侧血管扩张区（MCVA））中继至新的丘脑底区（丘脑底血管扩张区（SVA））。血管舒张剂通路（RVLM-MCVA-SVA）及其元件也可参与启动与rCGU偶联的皮质rCBF的升高;即，我们提出皮质血管舒张可能是由一群皮质血管舒张神经元介导的，这些神经元也由脑干通路兴奋。提出了两项研究。研究1采用放射自显影法测量rCBF和rCGU，电刺激或化学刺激或阻断，细胞外记录结合细胞外染色，通过证明（a）MCVA刺激、RVLM缺氧兴奋、缺氧和触须刺激兴奋SVA神经元，验证了SVA是血管扩张信号到皮层血管扩张神经元的主要中继的假设;（B）SVA的电刺激不依赖于rCGU而全面增加rCBF;以及（c）SVA神经元的损伤中断了由触须刺激引起的血管舒张，同时保留了体感皮层中的代谢变化。研究2使用细胞外和细胞内电生理记录和染色技术来测试以下假设：通过皮层传入投射兴奋的皮层神经元的特定亚群介导由RVLM-MCVA-SVA兴奋或体感刺激引起的血管舒张。这将通过（a）证明由MCVA的激发诱发的rCBF的增加依赖于局部皮层神经元的完整性;（B）证明由MCVA或SVA的刺激和缺氧诱发的皮层血管舒张本质上是神经源性的而不是血管源性的;（c）表征所声称的皮层血管舒张神经元的形态和生理特性;和（d）检查皮质血管扩张神经元本身是否是氧敏感的。

DESCRIPTION (provided by the applicant): The long-term objective of this study is to identify the neuronal pathways, and the cellular elements and functions, by which the brain regulates its own blood flow. It posits the existence of a dedicated cerebro-vasodilator network, which can elevate regional cerebral blood flow (rCBF) globally without parallel changes in local metabolism (regional cerebral glucose utilization, rCGU) as a primary vasodilation. This pathway (a) is closely linked to brainstem centers in the rostral ventrolateral medulla (RVLM) that sense and initiate elevations of rCBF in response to hypoxia; (b) is relayed through an adjacent area of the medulla, the medullary cerebro-vascular vasodilator area (MCVA), to a novel subthalamic area, the subthalamic vasodilator area (SVA). The vasodilator pathway (RVLM-MCVA-SVA) and its elements may also participate in initiating elevations of cortical rCBF that are coupled to rCGU; i.e., we propose that cortical vasodilation may be mediated by a population of cortical vasodilator neurons also excited by brainstem pathways. Two studies are proposed. Study 1, using autoradiographic measurement of rCBF and rCGU, electrical or chemical stimulation or blockade, and extracellular recording combined with juxtacellular staining, tests the hypothesis that SVA is a major relay of vasodilator signals to cortical vasodilator neurons by demonstrating that (a) SVA neurons are excited by MCVA stimulation, hypoxic excitation of RVLM, hypoxia, and vibrissa stimulation; (b) electrical stimulation of SVA globally increases rCBF independent of rCGU; and (c) lesions of SVA neurons interrupt the vasodilation elicited from vibrissa stimulation, while preserving metabolic changes in the somatosensory cortex. Study2 uses extra- and intracellular electrophysiological recording, and staining techniques to test the hypotheses that a specific subpopulation of cortical neurons excited through the cortical afferent projection mediates the vasodilation elicited by RVLM-MCVA-SVA excitation or somatosensory stimulation. This will be accomplished by (a) demonstrating that the increase in rCBF evoked by excitation of MCVA is dependent upon the integrity of local cortical neurons; (b) showing that cortical vasodilation evoked by stimulation of MCVA or SVA and hypoxia is neurogenic rather than vasogenic in nature (c) characterizing the morphological and physiological properties of purported cortical vasodilator neurons; and (d) examining whether cortical vasodilator neurons themselves are oxygen sensitive.