Brain and Spinal Cord Contributions to Anesthetic Action

描述(由申请人提供)我们的研究工作是针对 有助于阐明麻醉作用的解剖部位。我们早期的研究 表明异氟醚等麻醉剂会抑制运动反应 这发生在通过脊髓中的一个动作进行有害刺激之后。在……里面 在过去的资助周期中，我们确定了异氟醚和异丙酚在 脊髓抑制伤害性冲动的上行传递 大脑。这导致了由伤害性刺激引起的脑组织 脑电与丘脑和中脑的单位 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的中断 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)确定异氟醚 异丙酚在脊髓水平的作用会影响大脑的“觉醒”状态。 脑的MRF测量、桥脑脚被盖(PPT)和丘脑内侧 刺激对脑电的影响；2)测定神经递质 调节伤害性冲动上行传递到 大脑，以及异氟醚和异丙酚如何影响这些系统。我们假设 异氟醚和异丙酚可增加阈值刺激电流 引起脑电激活所需的MRF、PPT和内侧丘脑；2) 谷氨酸能激动剂、甘氨酸能拮抗剂和GABA能拮抗剂 应用于脊髓会增强，而谷氨酸能拮抗剂和 GABA能激动剂将抑制伤害性信息的上行传递 刺激大脑，从而引起脑电激活；3)异氟醚和 丙泊酚会间接抑制诱发的谷氨酸、天冬氨酸和乙酰胆碱， 但通过增加大脑皮层和内侧丘脑的GABA浓度 脊髓的一种作用。这些项目的成果将进一步推动我们的 异氟醚和异丙酚在体内发挥作用部位的认识 效果。这些信息将有助于开发更新、更安全的 麻醉药，以及导致临床上有用的手段来调节 神经递质系统本身是由麻醉剂调节的。

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.