Brain Injury During CPR Prevented by Vascular Nitroxide

血管氮氧化物预防心肺复苏期间的脑损伤

• 批准号: 6645128
• 负责人: Carleton Hsia
• 金额: $ 10万
• 依托单位: SYNZYME TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2004-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6645128
• 关键词: NMDA receptors; albumins; antioxidants; apoptosis; biotechnology; brain injury; cardiopulmonary resuscitation; colorimetry; disease /disorder prevention /control; drug screening /evaluation; electrophysiology; enzyme linked immunosorbent assay; heart arrest; hippocampus; iatrogenic disease; immunocytochemistry; laboratory rat; nervous system disorder therapy; neuroprotectants; nonhuman therapy evaluation; peptide chemical synthesis; serum albumin; statistics /biometry; synthetic protein

DESCRIPTION (provided by applicant): The brain damage that frequently accompanies cardiac arrest and resuscitation is devastating. Fewer than 10% of cardiopulmonary resuscitation (CPR) attempts result in survival without brain damage when treatment occurs in pre-hospital or a non-special care hospital environment (Safar, 1993). We propose that a novel vascular-compartmentalized nitroxide, polynitroxyl albumin (PNA), which is an enzyme-mimic antioxidant, can reduce brain damage after CPR. We present preliminary results in a CPR model showing PNA attenuates CA1 hippocampal cell loss 7 days after cardiac compression and resuscitation in rats. Published results also support this premise. In a middle cerebral artery occlusion model of stroke, mice treated with PNA were significantly protected against neural damage. We propose to further establish the cerebral protective activity of PNA in a cardiac compression model of CPR. Our specific aims are: 1) to address quality assurance issues in PNA production and in vitro documentation of efficacy, and 2) to compare the impact of PNA, human serum albumin (HSA) and saline treatment on the structure and function of the hippocampus. The end-points for the second aim will include measures of pyramidal cell viability, NMDA receptor 1 immunoreactivity, and in vitro electrophysiology of hippocampal slices. This combined morphological and electrophysiological approach in a whole body ischemia model should further document the value of PNA as a potent neuroprotectant. Attainment of these goals will fulfill the feasibility requirement for further study of PNA in a Phase II SBIR grant, which will emphasize dose response, extended time course, neurological recovery and the therapeutic index of PNA.

描述（由申请人提供）：经常伴随心脏骤停和复苏的脑损伤是毁灭性的。在院前或非特殊护理医院环境中发生治疗时，只有不到10％的心肺复苏（CPR）尝试导致无脑损伤生存（Safar，1993）。我们提出，一种新型的血管室化硝酸二氧化物蛋白（PNA）是一种酶模拟抗氧化剂，可以减少CPR后的脑损伤。我们在CPR模型中提出了初步结果，该模型显示PNA减弱了大鼠心脏压缩和复苏后的CA1海马细胞损失。已发布的结果也支持此前提。在中风中部动脉闭塞模型中，用PNA处理的小鼠受到明显保护的神经损伤。 我们建议在CPR的心脏压缩模型中进一步建立PNA的脑保护活性。我们的具体目的是：1）解决PNA生产和体外效力文献中的质量保证问题，以及2）比较PNA，人血清白蛋白（HSA）和盐水处理对海马的结构和功能的影响。第二个目标的终点将包括锥体细胞活力，NMDA受体1免疫反应性和海马切片的体外电生理学。在整个身体缺血模型中，这种结合的形态学和电生理方法应进一步记录PNA作为有效的神经保护剂的价值。实现这些目标将满足在II期SBIR赠款中进一步研究PNA的可行性要求，该赠款将强调剂量反应，延长的时间过程，神经系统恢复和PNA的治疗指数。