BRAIN FATTY ACID COMPOSITION AND THE ANESTHETIC EFFECT

在之前的工作中，我已经证明了大脑中的必需脂肪酸 缺乏(EFAD)增加啮齿动物对各种 挥发性麻醉剂，并降低他们对挥发物的敏感性 惊厥剂氟硫磷。挥发性麻醉剂敏感度增加 具体通过肠外补充方案(亚油酸)逆转 酸)，优先复制脑组织花生四烯酸含量 皮质多磷肌醇。我建议研究分子 EFAD改变麻醉剂/惊厥效力的机制，以及 从而深入了解挥发性物质的分子机制 麻醉/抽搐作用。为了达到这一目标，我提出了三个一般性的建议 研究领域：(1)通过研究 脑EFAD和挥发性麻醉剂/惊厥剂对脑电活动的影响 神经递质刺激的肌醇磷脂衍生化学物质的产生 第二信使(IP3、二酰甘油、花生四烯酸代谢物)。(2)至 通过确定EFAD对 非挥发性麻醉剂和惊厥剂的效力以及(3)确定 EFAD改变麻醉剂/惊厥剂和 使用核磁共振波谱技术的脑膜。这些研究的结果 三个调查领域应该提供关于 全动物麻醉/惊厥作用与神经元的关系(S) 化学成分和特定的生化和/或物理化学 麻醉剂/惊厥药的效果。

In previous work I have demonstrated that brain essential fatty acid deficiency (EFAD) increases the sensitivity of rodents to a variety of volatile anesthetics and decreases their sensitivity to the volatile convulsant fluorothyl. Increased volatile anesthetic sensitivity was specifically reversed by a parenteral supplementation protocol (linoleic acid) that preferentially repleted the arachidonic acid content of cerebral cortical polyphosphoinositides. I propose to study the molecular mechanisms through which EFAD alters anesthetic/convulsant potency, and thus to gain insight into the molecular mechanisms of volatile anesthetic/convulsant action. To reach this goal, I propose three general areas of study: (1) To pursue my preliminary observations by studying the effects of brain EFAD and of volatile anesthetics/convulsants on the neurotransmitter-stimulated generation of phosphoinositide derived chemical second messengers (IP3, diacylglycerol, arachidonate metabolites). (2) To further characterize the model by determining the effects of EFAD on the potency of non-volatile anesthetics and convulsants and (3) To determine if EFAD alters the chemical interaction between anesthetics/convulsants and brain membranes using NMR spectroscopic techniques. The results of these three areas of investigation should provide new insights concerning the relationship(s) between whole animal anesthetic/convulsant effect, neuronal chemical composition and specific biochemical and/or physicochemical effects of anesthetics/convulsants.