CEREBRAL PROTECTION & RECOVERY AFTER CIRCULATORY ARREST

大脑保护

• 批准号: 6499401
• 负责人: YAN XU
• 金额: $ 30.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6499401
• 关键词: AMPA receptors; NMDA receptors; adenosine triphosphate; antioxidants; artificial respiration; bioenergetics; body temperature; body water; brain circulation; brain metabolism; cardiopulmonary resuscitation; cerebral ischemia /hypoxia; cytotoxicity; disease /disorder model; heart arrest; histopathology; homeostasis; immunocytochemistry; laboratory rat; magnetic resonance imaging; neuroprotectants; neuropsychological tests; nuclear magnetic resonance spectroscopy

DESCRIPTION: (Adapted from the applicant's abstract) The PI proposes technologically intense, NMR/MRI based investigations of cardiac arrest using a new, clinically relevant rat cardiac arrest model. MRI/MRS data will be correlated with histopathologic and neurobehavioral outcomes. State-of-the-art interleaved multi-nuclear magnetic resonance spectroscopy and imaging are conducted in a customized 9.4 Tesla instrument with powerful gradient coils. Diffusion-weighted MR-imaging is used to detect rapid changes in brain edema, and spin-tagging of blood is used for perfusion imaging of the brain. Cardiac arrest will be induced by controlled asphyxiation in anesthetized, normothermic rats. Resuscitation will occur at four predetermined time points (12, 16, 20 and 24 minutes) after cardiac arrest. All events will occur inside a superwide-bore, 9.4 Tesla high-resolution NMR spectrometer, during which time MRI and MRS measurements will be continually made of rCBF, cerebral ion and water homeostasis, and brain metabolism. Measurements will be made before, during, and after cardiac arrest and resuscitation. Pre- and post-arrest pharmacological treatments will combine three classes of novel neuroprotective agents: (i) agents that improve cerebral energy metabolism, (ii) antioxidants that inhibit iron-dependent lipid peroxidation and key enzymes of the arachidonic acid cascade, and (iii) glutamate receptor antagonists that mitigate excitotoxicity injury. Seven series of experiments are proposed. The four specific aims are: (1) to correlate changes caused by global ischemia in cerebral perfusion, water homeostasis, and energy metabolism, with brain damage and neurologic outcome; (2) to correlate energy metabolism and water homeostasis with post-resuscitation hypoperfusion; (3) to study the effects of antioxidants on reperfusion injury; and (4) to study glutamate excitotoxicity in global ischemia.

描述：（根据申请人的摘要改编）PI提出了 基于技术激烈，基于NMR/MRI的心脏骤停研究 使用新的，临床上相关的大鼠心脏骤停模型。 MRI/MRS数据 将与组织病理学和神经行为结果相关。 最新的交织多核磁共振光谱 成像是在定制的9.4特斯拉仪器中进行的，具有功能强大 梯度线圈。 扩散加权MR成像用于检测快速 大脑水肿的变化和血液的旋转标记用于灌注 大脑的成像。 心脏骤停将通过受控诱导 麻醉的，常热的大鼠窒息。 复苏将发生 心脏后四个预定时间点（12、16、20和24分钟） 逮捕。 所有事件将发生在超级孔中，9.4特斯拉 高分辨率NMR光谱仪，在此期间MRI和MRS测量值 将不断由RCBF，脑离子和水稳态制成，以及 脑代谢。 测量将在之前，期间和之后进行 心脏骤停和复苏。 逮捕前后药理学 治疗将结合三类新型神经保护剂：（i） 改善脑能量代谢的药物，（ii）抗氧化剂 抑制铁核的铁依赖性脂质过氧化和关键酶 酸级联和（iii）谷氨酸受体拮抗剂减轻 兴奋性损伤。 提出了七个系列实验。 四个 具体目的是：（1）将全球性缺血引起的变化相关联 脑灌注，水稳态和能量代谢，大脑 损害和神经系统结果； （2）将能量代谢和水相关联 稳态，呼吸后灌注不足； （3）研究效果 再灌注损伤的抗氧化剂； （4）研究谷氨酸 全球缺血中的兴奋性毒性。