Bokesch P M, Marchand J, Seirafi P A, Deiss J M, Warner K G, Bronson R T, Kream R M
Department of Cardiothoracic Anesthesia, Cleveland Clinic Foundation, Ohio 44195, USA.
Anesthesiology. 1996 Dec;85(6):1439-46. doi: 10.1097/00000542-199612000-00026.
Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are associated with neurological injury. Altered immediate-early gene expression occurs rapidly in the brain in response to ischemia, hypoxia, and severe metabolic stress, which results in long-term changes in the molecular phenotype of neurons. This study determined the effects of CPB and HCA on the expression of the immediate-early gene c-fos.
Neonatal lambs were subjected to 2 h of CPB at 38 degrees C (n = 4) or 60 min (n = 6), 90 min (n = 7), and 120 min (n = 6) of HCA at 15 degrees C. One hour after terminating CPB at 38 degrees C, the brains were analyzed for FOS-encoding mRNA and FOS-like immunoreactivity in the hippocampal formation. Other animals (n = 15), subjected to the same CPB and HCA protocol, were allowed to survive 3-5 days before their brains were examined for dead neurons.
Minimal c-fos mRNA and FOS proteins were observed in neurons of animals subjected to normothermic bypass and of those that served as controls. Non-neuronal FOS proteins were observed in the choroid plexus, ependyma, and blood vessels at all times, including normothermic CPB, but not in the control animals without CPB. The magnitude of c-fos mRNA expression in hippocampal neurons increased directly with the duration of HCA. In contrast, expression of FOS proteins peaked after 90 min of HCA and declined significantly thereafter. Dead neurons were seen in surviving animals after 2 h of HCA only.
Cardiopulmonary bypass and HCA alter immediate-early gene expression in the brain. Translational processes are impaired after 120 min of HCA and correlate with neuron death in the hippocampus.
体外循环（CPB）和低温循环停搏（HCA）与神经损伤相关。即刻早期基因表达的改变在大脑中对缺血、缺氧和严重代谢应激的反应中迅速发生，这会导致神经元分子表型的长期变化。本研究确定了CPB和HCA对即刻早期基因c-fos表达的影响。
新生羔羊在38℃接受2小时的CPB（n = 4），或在15℃接受60分钟（n = 6）、90分钟（n = 7）和120分钟（n = 6）的HCA。在38℃的CPB结束1小时后，分析大脑海马结构中FOS编码mRNA和FOS样免疫反应性。其他动物（n = 15）接受相同的CPB和HCA方案，在其大脑检查死神经元之前存活3 - 5天。
在接受常温体外循环的动物和作为对照的动物的神经元中观察到极少的c-fos mRNA和FOS蛋白。在所有时间，包括常温CPB时，脉络丛、室管膜和血管中均观察到非神经元FOS蛋白，但在未进行CPB的对照动物中未观察到。海马神经元中c-fos mRNA表达的幅度直接随HCA持续时间增加。相比之下，FOS蛋白表达在HCA 90分钟后达到峰值，此后显著下降。仅在HCA 2小时后的存活动物中发现死神经元。
体外循环和HCA改变大脑中的即刻早期基因表达。HCA 120分钟后翻译过程受损，并与海马中的神经元死亡相关。
