Regulation of CBF by the Rostral Ventrolateral Medulla

描述(由申请人提供)：这项研究的长期目标是确定大脑调节自身血流的神经通路、细胞元素和功能。它假定存在一个专门的大脑-血管扩张剂网络，该网络可以在全球范围内提高局部脑血流量(RCBF)，而不会平行地改变局部代谢(局部脑葡萄糖利用，rCGU)作为主要的血管扩张。这条通路(A)与延髓头端腹外侧区(RVLM)的脑干中枢密切相关，后者感知并启动rCBF对低氧的反应；(B)通过延髓的邻近区域延髓脑血管扩张器区(MCVA)传递到新的丘脑下部区域(SVA)。血管扩张通路(RVLM-MCVA-SVA)及其元件也可能参与与rCGU偶联的皮质rCBF的升高，即我们认为皮质血管扩张可能是由一群同样由脑干通路兴奋的皮质血管扩张神经元介导的。提出了两项研究。研究1，采用放射自显影测量rCBF和rCGU，电或化学刺激或阻断，细胞外记录结合细胞外染色，验证了SVA是血管扩张信号到皮质血管扩张神经元的主要中继的假设，证明：(A)刺激MCVA，低氧兴奋RVLM，低氧和触须刺激SVA神经元；(B)全局电刺激SVA增加rCBF，而不依赖rCGU；(C)SVA神经元的损伤中断了由振动刺激引起的血管扩张，同时保留了躯体感觉皮质的代谢变化。研究2使用细胞外和细胞内的电生理记录和染色技术来检验这样的假设，即通过皮质传入投射兴奋的特定皮质神经元亚群介导了RVLM-MCVA-SVA兴奋或体感刺激所引起的血管扩张。这将通过以下方法实现：(A)证明刺激MCVA引起的rCBF增加依赖于局部皮质神经元的完整性；(B)证明刺激MCVA或SVA和低氧引起的皮质血管扩张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；以及(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.