Regulation of CBF by the Rostral Ventrolateral Medulla

描述（由申请人提供）：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、细胞成分和功能。它假设存在一个专用的脑血管舒张剂网络，它可以在不平行改变局部代谢（区域脑葡萄糖利用，rCGU）作为主要血管舒张的情况下提高区域脑血流量（rCBF）。这条通路(a)与位于延髓吻侧腹外侧（RVLM）的脑干中心密切相关，RVLM在缺氧时感知并启动rCBF的升高；(b)通过髓质的邻近区域，髓质脑血管血管舒张区（MCVA），传递到新的丘脑下区域，丘脑下血管舒张区（SVA）。血管舒张通路（RVLM-MCVA-SVA）及其元件也可能参与启动与rCGU相关的皮质rCBF升高；也就是说，我们提出皮质血管舒张可能是由脑干通路激发的皮质血管舒张神经元群介导的。提出了两项研究。研究1利用rCBF和rCGU的放射自显像测量、电刺激或化学刺激或阻断，以及结合细胞旁染色的细胞外记录，通过证明(a) SVA神经元在MCVA刺激、RVLM缺氧刺激、缺氧刺激和颤振刺激下兴奋，验证了SVA是血管扩张信号向皮质血管扩张神经元的主要中继的假设；(b) SVA电刺激整体增加rCBF，不依赖于rCGU；(c) SVA神经元的损伤中断了由触须刺激引起的血管舒张，同时保留了体感觉皮层的代谢变化。Study2使用细胞外和细胞内电生理记录和染色技术来验证通过皮层传入投射兴奋的特定皮层神经元亚群介导RVLM-MCVA-SVA兴奋或体感刺激引起的血管舒张的假设。这将通过(a)证明MCVA激发引起的rCBF的增加依赖于局部皮质神经元的完整性；(b)表明MCVA或SVA刺激和缺氧引起的皮质血管扩张在本质上是神经源性的，而不是血管源性的(c)表征所谓的皮质血管扩张神经元的形态和生理特性；(d)检查皮质血管扩张神经元本身是否对氧敏感。

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.