Vascular Regulatory Mechanisms of Palmitic Acid Methyl Ester

项目摘要 心脏骤停（CA）是美国死亡和残疾的主要原因。CA影响多达325，000人 只有10%的存活率。CA后的全身缺血导致随后的 脑损伤导致神经功能缺损我们的长期目标是通过恢复 脑血流量和随后与CA相关的神经功能缺损。因此， 了解CA诱导脑损伤的潜在机制。识别监管的重要性 影响脑血流自动调节的因素和创新的神经保护剂 CA对于改变CA之后的结果至关重要，这也是本提案的主要目标。我们建议 研究一种新的血管紧张素调节机制，释放棕榈酸甲酯（一种血管扩张剂， 神经保护剂）来源于支配主要脑动脉的上级颈神经节。我们的中央 假设是蛋白质精氨酸甲基转移酶是甲基化的调节“开关”， 棕榈酸甲酯在缺血期间负责血管舒张/神经保护。

Project Summary Cardiopulmonary arrest (CA) is a major cause of death and disability in the US. CA affects up to 325,000 people each year with only a 10% survival rate. The whole-body ischemia following CA results in subsequent brain damage resulting in neurological deficits. Our long-term goal is to decrease brain damage by reviving cerebral blood flow and subsequent neurological deficits associated with CA. Therefore, it is important to understand the mechanism(s) underlying CA-induced brain injury. The importance of identifying regulatory factors that influence cerebral blood flow autoregulation and innovative neuroprotective agents in the context of CA is paramount to change the outcomes following CA and it is the main goal of this proposal. We propose to study a new vasotone regulatory mechanism, the release of palmitic acid methyl ester (a vasodilator and neuroprotectant) derived from the superior cervical ganglion innervating major cerebral arteries. Our central hypothesis is that protein arginine methyltransferases are the regulatory “switch” for the methylation of palmitic acid to form palmitic acid methyl ester responsible for vasodilation/neuroprotection during ischemia.