Sugawara T, Kawase M, Lewén A, Noshita N, Gasche Y, Fujimura M, Chan P H
Department of Neurosurgery, Stanford University School of Medicine, 701B Welch Road, #148, Palo Alto, CA 94304, USA.
Brain Res. 2000 Sep 22;877(2):281-7. doi: 10.1016/s0006-8993(00)02684-6.
Neuronal death in the hippocampal CA1 subregion has been shown to occur in a delayed manner after transient global ischemia. The 2-vessel occlusion model is one of the most frequently used global ischemia paradigms in rodents. Although researchers often fail to induce bilateral delayed CA1 neuronal death, the importance of hypotension severity has not been fully discussed. We induced 10 min of global ischemia with 2-vessel occlusion and various severities of hypotension in rats, and the subsequent neuronal damage and neurogenesis in the hippocampal CA1 pyramidal cell layer were immunohistochemically studied. Neuronal apoptosis after global ischemia was also characterized by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL). The mean arterial blood pressure of 31-35 mmHg was the most appropriate range of hypotension in this model because of low mortality and consistent bilateral CA1 injury. Most of the neurons in the CA1 pyramidal cell layer lost neuron specific nuclear protein and became TUNEL-positive 3 days after ischemia. There was no evidence of apoptosis or neurogenesis at 7-28 days. There were ischemia-tolerant neurons in the CA1 pyramidal cell layer that survived delayed neurodegeneration, however, further studies are necessary to characterize the property of these neurons.
海马CA1亚区的神经元死亡已被证明在短暂性全脑缺血后呈延迟性发生。双血管闭塞模型是啮齿动物中最常用的全脑缺血范例之一。尽管研究人员常常未能诱导出双侧延迟性CA1神经元死亡，但低血压严重程度的重要性尚未得到充分讨论。我们在大鼠中通过双血管闭塞诱导10分钟的全脑缺血以及不同严重程度的低血压，并对海马CA1锥体细胞层随后的神经元损伤和神经发生进行了免疫组织化学研究。全脑缺血后的神经元凋亡也通过末端脱氧核苷酸转移酶介导的尿苷5'-三磷酸生物素缺口末端标记（TUNEL）进行表征。在该模型中，平均动脉血压为31 - 35 mmHg是最合适的低血压范围，因为死亡率低且双侧CA1损伤一致。缺血3天后，CA1锥体细胞层中的大多数神经元失去神经元特异性核蛋白并变为TUNEL阳性。在7 - 28天没有凋亡或神经发生的证据。CA1锥体细胞层中有耐缺血神经元在延迟性神经变性中存活下来，然而，需要进一步研究来表征这些神经元的特性。
