Ostrowski Robert P, Graupner Gerhart, Titova Elena, Zhang Jennifer, Chiu Jeffrey, Dach Neal, Corleone Dalia, Tang Jiping, Zhang John H
Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Neurobiol Dis. 2008 Jan;29(1):1-13. doi: 10.1016/j.nbd.2007.07.020. Epub 2007 Jul 28.
We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague-Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 min of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.
我们假设,在短暂性全脑缺血大鼠模型中,高压氧(HBO)预处理的脑保护作用是通过抑制早期凋亡来介导的。将110只雄性Sprague-Dawley(SD)大鼠(体重300 - 350克)分为假手术组和其他三组,后三组进行10分钟的四动脉闭塞手术,其中一组不进行处理,另外两组分别用3次或5次高压氧预处理。HBO预处理改善了神经行为评分并降低了死亡率,减少了缺血性细胞变化,减少了早期凋亡细胞的数量,并阻碍了早期凋亡向晚期凋亡改变的转变。HBO预处理降低了易损神经元中磷酸化p38的免疫反应性,并增加了缺血后早期脑源性神经营养因子(BDNF)的表达。然而,3次HBO治疗预处理的效果不如5次HBO治疗预处理。我们得出结论,HBO预处理可能通过减少早期凋亡和抑制早期凋亡向晚期凋亡的转变而具有神经保护作用,这可能是通过增加脑BDNF水平和抑制p38激活来实现的。