Unal I, Gürsoy-Ozdemir Y, Bolay H, Söylemezoglu F, Saribaş O, Dalkara T
Department of Neurology, Faculty of Medicine and Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100, Ankara, Turkey.
Brain Res. 2001 Nov 2;917(2):174-81. doi: 10.1016/s0006-8993(01)02914-6.
Brief cerebral ischemia is reported to cause selective neuronal necrosis, apoptotic cell death, silent infarcts and, when recurrent, cognitive decline. Acute administration of selegiline and EGb 761 have been shown to have anti-apoptotic and neuroprotective effects in experimental ischemia. Their daily use is currently advised to slow down cognitive decline in patients with vascular dementia. Hence, unlike previous studies, we studied the neuroprotective action of chronic daily administration of these drugs in Swiss mice subjected to 30-min middle cerebral artery occlusion and 72 h of reperfusion since this model was reported to induce a slowly evolving infarct with profuse apoptotic cell death. Infarct area was evaluated by H&E staining on coronal brain sections and, apoptotic cells were identified by histological criteria, terminal transferase-mediated d-UTP nick-end labeling (TUNEL) and by immunohistochemical detection of caspase-cleaved actin fragments (fractin). Fifty-one mice received daily intraperitoneal injections of 10 mg/kg selegiline (n=18) or 50 mg/kg EGb 761 (n=17) or equal volume of saline (n=16) for 10-14 days before but not on the day of insult. The infarct volume, number of TUNEL- and fractin-positive cells were significantly reduced in treatment groups by 30, 42 and 51% (selegiline) and, 27, 27 and 29% (EGb 761), respectively. These data suggest that prophylactic use of selegiline and EGb 761 could increase the brain's resistance to mild ischemic injury.
据报道，短暂性脑缺血会导致选择性神经元坏死、凋亡性细胞死亡、无症状性梗死，反复发生时还会导致认知能力下降。在实验性缺血中，司来吉兰和银杏叶提取物EGb 761急性给药已显示出抗凋亡和神经保护作用。目前建议每日使用这些药物以减缓血管性痴呆患者的认知能力下降。因此，与以往的研究不同，我们研究了在瑞士小鼠中每日长期给药这些药物的神经保护作用，这些小鼠经历了30分钟的大脑中动脉闭塞和72小时的再灌注，因为据报道该模型会诱导缓慢发展的梗死并伴有大量凋亡性细胞死亡。通过对冠状脑切片进行苏木精-伊红（H&E）染色评估梗死面积，并根据组织学标准、末端转移酶介导的d-UTP缺口末端标记（TUNEL）以及通过免疫组织化学检测半胱天冬酶切割的肌动蛋白片段（fractin）来鉴定凋亡细胞。51只小鼠在损伤前10 - 14天（而非损伤当天）每天接受腹腔注射10 mg/kg司来吉兰（n = 18）或50 mg/kg EGb 761（n = 17）或等量的生理盐水（n = 16）。治疗组的梗死体积、TUNEL阳性细胞数和fractin阳性细胞数分别显著减少了30%、42%和51%（司来吉兰组）以及27%、27%和29%（EGb 761组）。这些数据表明，预防性使用司来吉兰和EGb 761可以增加大脑对轻度缺血性损伤的抵抗力。
