Järvelä Juha T, Lopez-Picon Francisco R, Holopainen Irma E
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland.
Epilepsia. 2008 May;49(5):832-41. doi: 10.1111/j.1528-1167.2007.01454.x. Epub 2007 Dec 10.
Epileptic seizures lead to age-dependent neuronal damage in the developing brain, particularly in the hippocampus, but the mechanisms involved have remained poorly elucidated. In this study, we investigated the contribution of apoptosis and inflammatory processes to neuronal damage after status epilepticus (SE) in postnatal rats.
SE was induced by an intraperitoneal injection of kainic acid (KA) in 21- and 9-day-old (P21 and P9) rats. The expression of Bax, Bcl-2 and caspase-3, markers for apoptosis, and cyclooxygenase-2 (COX-2), an indicator for activation of inflammatory processes, were studied from 6 h up to 1 week after SE by Western blotting and immunocytochemistry. Neuronal damage was verified by Fluoro-Jade B staining.
In P21 rats, SE resulted in neuronal damage in the CA1 neurons of the hippocampus. COX-2 expression was extensively, but transiently, increased and its immunoreactivity pronouncedly enhanced in several hippocampal subregions, amygdala, and piriform cortex by 24 h after SE. The expression of Bax and caspase-3 remained unchanged, whereas the antiapoptotic factor Bcl-2 transiently decreased by 24 h. Single caspase-3 positive neurons appeared in the CA1 region of both control and KA-treated rats. In P9 rats, no neuronal death was detected, and COX-2 expression and immunoreactivity remained at the control level.
Our results suggest that SE provokes age-specific effects on COX-2 expression. This together with the activation of putative inflammatory processes may contribute to neuronal cell death in the hippocampus of postnatal rats, whereas caspase-dependent apoptosis seems not to be involved in the death process.
癫痫发作会导致发育中的大脑，尤其是海马体出现年龄依赖性神经元损伤，但其涉及的机制仍未完全阐明。在本研究中，我们调查了凋亡和炎症过程在新生大鼠癫痫持续状态（SE）后神经元损伤中的作用。
通过腹腔注射海藻酸（KA）诱导21日龄和9日龄（P21和P9）大鼠发生SE。在SE后6小时至1周，通过蛋白质免疫印迹法和免疫细胞化学研究凋亡标志物Bax、Bcl-2和caspase-3以及炎症过程激活指标环氧合酶-2（COX-2）的表达。通过Fluoro-Jade B染色验证神经元损伤。
在P21大鼠中，SE导致海马体CA1神经元损伤。SE后24小时，COX-2表达广泛但短暂增加，其免疫反应性在几个海马亚区、杏仁核和梨状皮质中明显增强。Bax和caspase-3的表达保持不变，而抗凋亡因子Bcl-2在24小时时短暂下降。在对照大鼠和KA处理的大鼠的CA1区域均出现单个caspase-3阳性神经元。在P9大鼠中，未检测到神经元死亡，COX-2表达和免疫反应性保持在对照水平。
我们的结果表明，SE对COX-2表达产生年龄特异性影响。这与假定的炎症过程激活一起，可能导致新生大鼠海马体中的神经元细胞死亡，而caspase依赖性凋亡似乎不参与死亡过程。
