Brain and Spinal Cord Contributions to Anesthetic Action

描述（由申请人提供）我们的研究工作一直针对 以阐明麻醉作用的解剖部位。我们早期的研究 表明麻醉剂如异氟醚抑制运动反应 脊髓受到伤害性刺激后产生的疼痛在 在过去的格兰特周期中，我们确定了异氟烷和丙泊酚在 脊髓抑制了伤害性冲动向脊髓的上行传递， 个脑袋这导致了对神经元的伤害性激活的消融。 脑电图（EEG）和丘脑和中脑的单个单位 网状结构（MRF）。因为MRF和丘脑对于 意识和记忆，很可能是伤害性输入中断， 这些部位降低了意识和记忆形成的可能性 在麻醉期间。在这项提案中，我们的目标是：1）确定异氟烷是否 异丙酚在脊髓水平的作用会影响脊髓的“唤醒”状态， 大脑，通过MRF、脚桥被盖（PPT）和内侧丘脑测量 对EEG的刺激诱导效应; 2）确定神经递质 调节伤害性冲动上行传递至 以及异氟烷和丙泊酚如何影响这些系统。我们假设 异氟醚和丙泊酚会增加阈值刺激电流 在MRF、PPT和内侧丘脑中需要引起EEG激活; 2） 谷氨酸能激动剂、甘氨酸能拮抗剂和GABA能拮抗剂 应用于脊髓将增强，而多巴胺能拮抗剂， GABA能激动剂将抑制伤害性信息的上行传递， 脉冲到大脑，从而引起EEG激活; 3）异氟烷， 丙泊酚将间接抑制诱发的谷氨酸、天冬氨酸和乙酰胆碱， 但通过增强大脑皮层和丘脑内侧的GABA浓度， 脊髓的活动这些项目的成果将进一步推动我们的 了解异氟烷和丙泊酚发挥其 方面的影响.这些信息将有助于开发更新，更安全的 麻醉剂，以及导致临床上有用的手段，调节 神经递质系统本身由麻醉剂调节。

DESCRIPTION (provided by applicant) Our research efforts have been directed towards elucidation of anatomic sites of anesthetic action. Our earlier studies indicated that anesthetics such as isoflurane depress the movement response that occurs following noxious stimulation via an action in the spinal cord. In the past grant cycle we determined that isoflurane and propofol action in the spinal cord depressed the ascending transmission of nociceptive impulses to the brain. This resulted in ablation of the noxious-evoked activation of the electroencephalogram (EEG) and single-units in the thalamus and midbrain reticular formation (MRF). Because the MRF and thalamus are critical to consciousness and memory, it is likely that disruption of nociceptive input to these sites decreases the likelihood of consciousness and memory formation during anesthesia. In this proposal we aim to 1) determine whether isoflurane and propofol action at the spinal level affects the "arousal" state of the brain, as measured by MRF, pedunculopontine tegmental (PPT) and medial thalamic stimulation-induced effects on the EEG; 2) determine the neurotransmitter systems that modulate the ascending transmission of nociceptive impulses to the brain, and how isoflurane and propofol affect these systems. We hypothesize that 1) isoflurane and propofol will increase the threshold stimulation current in the MRF, PPT and medial thalamus required to cause EEG activation; 2) glutamatergic agonists, glycinergic antagonists and GABAergic antagonists applied to the spinal cord will enhance, while glutamatergic antagonists and GABAergic agonists will depress, the ascending transmission of nociceptive impulses to the brain, and thereby cause EEG activation; 3) isoflurane and propofol will indirectly depress evoked glutamate, aspartate and acetylcholine, but enhance GABA concentrations in the cerebral cortex and medial thalamus via an action in the spinal cord. The results of these projects will further our understanding of the in vivo sites where isoflurane and propofol exert their effects. This information will aid the development of newer and safer anesthetics, as well as lead to clinically useful means of modulating the neurotransmitter systems that are themselves modulated by anesthetics.