CEREBRAL PROTECTION & RECOVERY AFTER CIRCULATORY ARREST

描述：(改编自申请者的摘要)PI建议 技术密集、基于核磁共振/磁共振成像的心脏骤停研究 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。 最新的交错多核磁共振波谱学 和成像在定制的9.4特斯拉仪器中进行，具有强大的 渐变线圈。磁共振扩散加权成像用于快速检测 脑水肿的变化和血液的自旋标记用于灌流 大脑的成像。心脏骤停将由受控诱导 麻醉常温大鼠窒息。复苏将会发生 在心脏手术后的四个预定时间点(12、16、20和24分钟) 逮捕。所有活动都将在9.4特斯拉的超宽口径内进行 高分辨率核磁共振波谱仪，在此期间进行MRI和MRS测量 将继续由rCBF、脑离子和水的动态平衡组成，以及 大脑新陈代谢。测量将在之前、期间和之后进行 心脏骤停和复苏。逮捕前和逮捕后药理学 治疗将结合三类新型神经保护剂：(I) 改善大脑能量代谢的药物，(Ii)抗氧化剂 抑制铁依赖的脂质过氧化和花生四烯酸关键酶 酸级联，以及(Iii)谷氨酸受体拮抗剂 兴奋性毒性损伤。提出了七个系列的实验方案。四个 具体目标是：(1)将全球缺血引起的变化与 脑血流、水平衡和能量代谢，与脑 损伤与神经转归；(2)能量代谢与水分的关系 复苏后低灌注组的动态平衡；(3)研究复苏后低灌注组的影响 抗氧化剂对再灌注损伤的作用；以及(4)研究谷氨酸 全脑缺血的兴奋性毒性。

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.