CEREBRAL PROTECTION & RECOVERY AFTER CIRCULATORY ARREST

大脑保护

• 批准号: 6135736
• 负责人: YAN XU
• 金额: $ 5.6万
• 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 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6135736
• 关键词: AMPA receptors; NMDA receptors; adenosine triphosphate; antioxidants; artificial respiration; bioenergetics; body temperature; body water; 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：（改编自申请人摘要）PI建议 基于核磁共振/核磁共振成像的技术密集型心脏骤停研究 使用一种新的临床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。 最先进的交错多核磁共振波谱技术 在定制的9.4特斯拉仪器中进行成像， 梯度线圈 弥散加权磁共振成像用于检测快速 脑水肿的变化，血液自旋标记用于灌注 大脑成像。 心脏骤停将通过控制 窒息在麻醉，常温大鼠。 复苏将会发生 在心脏起搏后的四个预定时间点（12、16、20和24分钟）， 逮捕了 所有事件都将发生在一个9.4特斯拉的超大口径 高分辨率NMR光谱仪，在此期间，MRI和MRS测量 将持续由rCBF、脑离子和水稳态组成， 脑代谢 测量将在之前、期间和之后进行 心脏骤停和复苏 停搏前和停搏后药理学 治疗将结合联合收割机三类新的神经保护剂：（i） 改善脑能量代谢的药剂，（ii）抗氧化剂， 抑制铁依赖性脂质过氧化和花生四烯酸关键酶 酸级联，和（iii）谷氨酸受体拮抗剂，其减轻 兴奋性毒性损伤 提出了七个系列的实验。 四 具体的目的是：（1）将由全脑缺血引起的变化与 脑灌注、水稳态和能量代谢， 损害和神经功能的结果;（2）能量代谢和水的相关性 复苏后低灌注状态下的体内平衡;（3）研究复苏后低灌注状态下， 抗氧化剂对再灌注损伤的影响;（4）研究谷氨酸 兴奋性毒性。