Garry P S, Ezra M, Rowland M J, Westbrook J, Pattinson K T S
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Exp Neurol. 2015 Jan;263:235-43. doi: 10.1016/j.expneurol.2014.10.017. Epub 2014 Oct 29.
Nitric oxide (NO) is a key signalling molecule in the regulation of cerebral blood flow. This review summarises current evidence regarding the role of NO in the regulation of cerebral blood flow at rest, under physiological conditions, and after brain injury, focusing on subarachnoid haemorrhage, traumatic brain injury, and ischaemic stroke and following cardiac arrest. We also review the role of NO in the response to hypoxic insult in the developing brain. NO depletion in ischaemic brain tissue plays a pivotal role in the development of subsequent morbidity and mortality through microcirculatory disturbance and disordered blood flow regulation. NO derived from endothelial nitric oxide synthase (eNOS) appears to have neuroprotective properties. However NO derived from inducible nitric oxide synthase (iNOS) may have neurotoxic effects. Cerebral NO donor agents, for example sodium nitrite, appear to replicate the effects of eNOS derived NO, and therefore have neuroprotective properties. This is true in both the adult and immature brain. We conclude that these agents should be further investigated as targeted pharmacotherapy to protect against secondary brain injury.
一氧化氮（NO）是调节脑血流量的关键信号分子。本综述总结了关于NO在静息状态、生理条件下以及脑损伤后（重点关注蛛网膜下腔出血、创伤性脑损伤、缺血性卒中和心脏骤停后）调节脑血流量作用的当前证据。我们还综述了NO在发育中脑对缺氧损伤反应中的作用。缺血脑组织中NO的耗竭通过微循环紊乱和血流调节失调在随后的发病和死亡发展中起关键作用。源自内皮型一氧化氮合酶（eNOS）的NO似乎具有神经保护特性。然而，源自诱导型一氧化氮合酶（iNOS）的NO可能具有神经毒性作用。脑NO供体药物，例如亚硝酸钠，似乎能复制源自eNOS的NO的作用，因此具有神经保护特性。这在成年脑和未成熟脑中均如此。我们得出结论，这些药物应作为针对继发性脑损伤的靶向药物疗法进行进一步研究。
