White B C, Grossman L I, O'Neil B J, DeGracia D J, Neumar R W, Rafols J A, Krause G S
Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.
Ann Emerg Med. 1996 May;27(5):588-94. doi: 10.1016/s0196-0644(96)70161-0.
Brain damage accompanying cardiac arrest and resuscitation is frequent and devastating. Neurons in the hippocampus CA1 and CA4 zones and cortical layers III and V are selectively vulnerable to death after injury by ischemia and reperfusion. Ultrastructural evidence indicates that most of the structural damage is associated with reperfusion, during which the vulnerable neurons develop disaggregation of polyribosomes, peroxidative damage to unsaturated fatty acids in the plasma membrane, and prominent alterations in the structure of the Golgi apparatus that is responsible for membrane assembly. Reperfusion is also associated with vulnerable neurons with prominent production of messenger RNAs for stress proteins and for the proteins of the activator protein-1 complex, but these vulnerable neurons fail to efficiently translate these messages into the proteins. The inhibition of protein synthesis during reperfusion involves alteration of translation initiation factors, specifically serine phosphorylation of the alpha-subunit of eukaryotic initiation factor-2 (elF-2 alpha). Growth factors--in particular, insulin--have the potential to reverse phosphorylation of elF-2 alpha, promote effective translation of the mRNA transcripts generated in response to ischemia and reperfusion, enhance neuronal defenses against radicals, and stimulate lipid synthesis and membrane repair. There is now substantial evidence that the insulin-class growth factors have neuron-sparing effects against damage by radicals and ischemia and reperfusion. This new knowledge may provide a fundamental basis for a rational approach to "cerebral resuscitation" that will allow substantial amelioration of the often dismal neurologic outcome now associated with resuscitation from cardiac arrest.
心脏骤停及复苏过程中伴随的脑损伤很常见且具有毁灭性。海马体CA1和CA4区以及皮质层III和V的神经元在经历缺血和再灌注损伤后，特别容易死亡。超微结构证据表明，大部分结构损伤与再灌注有关，在此期间，易损神经元会出现多核糖体解聚、质膜中不饱和脂肪酸的过氧化损伤，以及负责膜组装的高尔基体结构的显著改变。再灌注还与易损神经元有关，这些神经元会大量产生应激蛋白和激活蛋白-1复合物的蛋白质的信使核糖核酸，但这些易损神经元无法有效地将这些信息翻译成蛋白质。再灌注期间蛋白质合成的抑制涉及翻译起始因子的改变，特别是真核起始因子-2（elF-2α）α亚基的丝氨酸磷酸化。生长因子——尤其是胰岛素——有可能逆转elF-2α的磷酸化，促进对缺血和再灌注产生的信使核糖核酸转录本的有效翻译，增强神经元对自由基的防御能力，并刺激脂质合成和膜修复。现在有大量证据表明，胰岛素类生长因子对自由基、缺血和再灌注造成的损伤具有神经保护作用。这一新知识可能为“脑复苏”的合理方法提供一个基本依据，从而能够显著改善目前与心脏骤停复苏相关的往往令人沮丧的神经学结果。
