Thornton Claire, Rousset Catherine I, Kichev Anton, Miyakuni Yasuka, Vontell Regina, Baburamani Ana A, Fleiss Bobbi, Gressens Pierre, Hagberg Henrik
Centre for the Developing Brain, Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Neurol Res Int. 2012;2012:506320. doi: 10.1155/2012/506320. Epub 2012 Jan 26.
Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult.
胎儿/新生儿脑损伤是神经残疾的重要原因。缺氧缺血和兴奋性毒性被认为是重要的损伤因素，尽管它们具有急性性质，但脑损伤在原发性、继发性和第三阶段的较长时间内发展。大多数损伤在损伤后延迟发生的概念使得在损伤后提供有效的神经保护治疗成为可能。事实上，在新生儿脑病出生后6小时内进行低温治疗可降低临床试验中的神经残疾。为了开发下一代治疗方法，我们需要更多地了解损伤继发性和第三阶段的病理生理机制。我们回顾了一些与继发性阶段线粒体功能障碍和细胞凋亡相关的关键分子事件，并报告了一些最近的证据，表明在损伤后数天至数周进行干预也是可行的。
