NORADRENERGIC CONTROL OF CEREBRAL METABOLISM

我们的目标是继续研究内源性的生物学作用， 脑去甲肾上腺素在脑代谢调控中的作用及其局部 微血管灌注和毛细血管通透性。 生理 去甲肾上腺素对脑功能影响的潜在机制 并且它们在异常病理生理条件下的意义将是 研究了 结果是以前从这个实验室获得的 为这种作用提供了充分的证据，特别是当大脑代谢 需要增加，并且在病理生理条件下， 如高血压癫痫和脑缺血 选择的范例之一 因为这些研究包括核的单侧化学损伤 大鼠的蓝斑。 蓝斑是大多数 大脑皮层和海马体的去甲肾上腺素能神经支配。 将使用以下组合研究蓝斑病变的影响： 生理学、生物化学、药理学和形态学方法， 体外和体内。 生理学研究将测量脑血流量 和毛细血管通透性，并将决定是否去甲肾上腺素能 脑循环的神经支配在毛细血管中起作用 招募和维持血脑屏障的完整性。 血脑屏障的功能将通过其以下能力来评估 阻止大分子如白蛋白进入大脑， 水和电解质从血液到大脑的主动运输， 亦然 生物化学和形态学方法将用于研究 去甲肾上腺素能受体对消融假定的 脑血管的去甲肾上腺素能神经支配， 大脑补偿慢性去甲肾上腺素能神经支配后， 蓝斑病变恢复功能。 这些实验将 揭示了导致复苏的因素的性质， 的功能，并将提供有关的现象， 可塑性，再生和发芽在成年哺乳动物的大脑。

Our aim is to continue the study of the biological role of endogenous cerebral norepinephrine in the control of brain metabolism and its local microvascular perfusion and capillary permeability. The physiological mechanisms underlying this influence of norepinephrine on brain function and their significance in abnormal pathophysiological conditions will be investigated. The results is previously obtained from this laboratory provide ample evidence for such a role, especially when cerebral metabolic requirements are increased, and during pathophysiological conditions such as hypertension, epilepsy, and brain ischemia. One of the paradigms chosen for these studies include the unilateral chemical lesion of the nucleus ceruleus in the rat. The locus ceruleus is the site of origin of most of the noradrenergic innervation of the cerebral cortex and hippocampus. Effects of locus ceruleus lesion will be studied using a combination of physiological, biochemical, pharmacological, and morphological methods in vitro and in vivo. Physiological studies will measure cerebral blood flow and capillary permeability, and will determine whether the noradrenergic innervation of the cerebral circulation plays a role in capillary recruitment and in maintaining the integrity of the blood-brain barrier. Functions of the blood-brain barrier will be assessed by its ability to exclude large molecules such as albumin from entering the brain, and by the active transport of water and electrolytes from blood-to-brain and vice versa. Biochemical and morphological methods will be used to study the response of noradrenergic receptors to the ablation of the putative noradrenergic innervation of cerebral blood vessels, and the mechanisms by which the brain compensates for chronic noradrenergic denervation after locus ceruleus lesion to restitute function. These latter experiments will shed light on the nature of factors that are responsible for the recovery of function, and will provide basic information regarding the phenomena of plasticity, regeneration, and sprouting in the adult mammalian brain.