Berger Richard, Middelanis Johannes, Vaihinger Hans-Martin, Mies Guenter, Wilken Bernd, Jensen Arne
Department of Obstetrics and Gynecology, University of Bochum, Bochum, Germany.
J Soc Gynecol Investig. 2004 Jan;11(1):9-15. doi: 10.1016/j.jsgi.2003.07.002.
We tested the neuroprotective effects of creatine against hypoxic-ischemic injury in the immature brain.
Hippocampal slices were prepared from fetal guinea pigs at 0.9 gestation and incubated in artificial cerebrospinal fluid (aCSF) equilibrated with carbogen. Slices were subjected to oxygen-glucose deprivation (OGD) for 30 or 40 minutes. Two hours after OGD, adenosine triphosphate (ATP) and protein synthesis were analyzed. Creatine (3 mM) was applied to tissue slices of the study groups 2 hours before the insult. In a second set of experiments 7-day-old Wistar rats were anesthetized, and the left carotid artery was ligated. After 1 hour of recovery the pups were subjected to a hypoxic gas mixture (8% oxygen and 92% nitrogen) for 80 minutes. Seven days later the brains of the neonates were removed and analyzed for hypoxic-ischemic injury. The rat pups of the test group were treated with creatine (3 g/kg subcutaneously) before (-64 hours, -40 hours, and -16 hours) and after (+3 hours) the hypoxic-ischemic insult, with zero time corresponding to the start of hypoxia, whereas the animals of the control group received the solvent.
Creatine significantly improved the recovery of protein synthesis 2 hours after OGD in hippocampal slices but had no effect on ATP levels. Whereas seven animals of the control group developed severe cystic cerebral infarction, only mild to moderate damage was observed in the rat pups of the study group. In contrast to creatine-treated pups, the volume of the ipsilateral hemisphere was considerably smaller than that of the contralateral one in control animals (104 +/- 22 versus 138 +/- 14 mL, P<.001). Except at the frontal level (A 6.0 mm), neuronal cell injury was significantly lower in the cortex of the animals that had received creatine. This was also true for the evaluated subfields in the hippocampus.
We conclude that creatine protects the immature brain from hypoxic-ischemic injury.
我们测试了肌酸对未成熟脑缺氧缺血性损伤的神经保护作用。
从妊娠0.9期的胎豚鼠制备海马切片，并在与卡波金平衡的人工脑脊液（aCSF）中孵育。将切片进行30或40分钟的氧糖剥夺（OGD）。OGD后两小时，分析三磷酸腺苷（ATP）和蛋白质合成。在损伤前两小时将肌酸（3 mM）应用于研究组的组织切片。在第二组实验中，将7日龄的Wistar大鼠麻醉，结扎左颈动脉。恢复1小时后，将幼崽置于低氧气体混合物（8%氧气和92%氮气）中80分钟。七天后，取出新生儿的大脑并分析缺氧缺血性损伤。测试组的幼鼠在缺氧缺血性损伤前（-64小时、-40小时和-16小时）和后（+3小时）用肌酸（3 g/kg皮下注射）治疗，零时间对应于缺氧开始，而对照组动物接受溶剂。
肌酸显著改善了OGD后两小时海马切片中蛋白质合成的恢复，但对ATP水平无影响。对照组的七只动物发生了严重的囊性脑梗死，而研究组的幼鼠仅观察到轻度至中度损伤。与用肌酸治疗的幼崽相比，对照组动物同侧半球的体积明显小于对侧半球（104±22对138±14 mL，P<0.001）。除额叶水平（A 6.0 mm）外，接受肌酸的动物皮质中的神经元细胞损伤明显较低。海马体中评估的子区域也是如此。
我们得出结论，肌酸可保护未成熟脑免受缺氧缺血性损伤。
