ANESTHETICS AND STRESS PROTEINS IN BRAIN CELL INJURY

描述：（改编自申请人摘要） 麻醉师经常管理有脑血管病风险的患者。 缺血和麻醉剂长期以来一直被研究为潜在的 神经保护剂因为脑缺血引起的变化 是细胞机制，简化模型系统补充 动物研究通过允许分析细胞机制。 确定麻醉剂对脑细胞的细胞效应， 缺血将导致更好地理解病理生理学 缺血性脑损伤 新的治疗选择可能会 这是由于对缺血的细胞生物学理解的提高。 最近，通过预先诱导a 报告了应激反应。 首先描述的是对热的反应， “热休克”或“应激”蛋白质的产生反映了一种协调的 基因表达的变化，以应对不同的环境 包括局部缺血。 在热的情况下，这种反应是 由于转录因子（HSF）的激活， 协调激活应激基因。 神经元的已知能力 和星形胶质细胞来进行应激反应， 他们对伤害的脆弱性。然而，压力的机制 在大脑中的反应诱导和它的保护作用是不是 明确定义。此外，麻醉剂对 细胞应激反应实际上是未知的。 申请人 建议在神经元的原代培养中解决这些问题， 星形胶质细胞研究作为应激反应代表的HSP 70。 (1)神经元转录诱导的机制和 通过OGD（体外缺血）测定星形胶质细胞。 (2)是否 一些麻醉剂单独诱导HSP 70，以及它们是否改变HSP 70 在星形胶质细胞或神经元中响应于局部缺血的产生将是 测定 (3)热预处理可保护脑细胞免受 热休克蛋白70在这种保护中的重要性将 用反义RNA阻断hsp70的产生。 (4)的 特定类型的损伤诱导HSP 70的相对功效将是 测定 这些研究将有助于确定诱导机制 热休克蛋白70及其可能的重要性，在保护神经元， 星形胶质细胞的损伤。

DESCRIPTION: (Adapted from the applicant's abstract) Anesthesiologists frequently manage patients at risk of cerebral ischemia, and anesthetics have long been studied as potential neuroprotectants. Because the changes provoked by cerebral ischemia are cellular mechanisms, simplified model systems complement animal studies by allowing analysis of cellular mechanisms. Defining the cellular effects of anesthetics on brain cells during ischemia will lead to a better understanding of the pathophysiology of ischemic brain injury. New therapeutic options will likely result from improved understanding of the cell biology of ischemia. Recently, brain protection from ischemia by prior induction of a stress response was reported. First described in response to heat, "heat shock" or "stress" protein production reflects a coordinated change in gene expression in response to diverse environmental stresses, including ischemia. This response, in the case of heat, is due to activation of a transcription factor (HSF) which leads to coordinated activation of stress genes. The known ability of neurons and astrocytes to mount a stress response is proposed to modulate their vulnerability to injury. However, the mechanism of stress response induction in the brain and its role in protection is not clearly defined.Furthermore, the effect of anesthetics on the cellular stress response is virtually unknown. The applicants propose to address these problems in primary cultures of neurons and astrocytes studying hsp70 as representative of the stress response. (1) The mechanisms of induction of transcription in neurons and astrocytes by OGD (in vitro ischemia) will be determined. (2) Whether some anesthetics alone induce hsp70 and whether they alter hsp70 production in astrocytes or neurons in response to ischemia will be determined. (3) Pretreatment with heat protects brain cells from subsequent ischemia; the importance of hsp70 in this protection will be evaluated using antisense RNA to block hsp70 production. (4) The relative efficacy of specific types of injury to induce hsp70 will be determined. These studies will help define the mechanism of induction of hsp70 and its possible importance in protecting neurons and astrocytes from OGD injury.