Mao Ding-An, Yin Qun, Liu Li-Qun, Bo Tao, Bai Hai-Tao, Xiong Jie
Department of Pediatrics, Second Xiangya Hospital of Central South University, Changsha 410011.
Zhongguo Dang Dai Er Ke Za Zhi. 2006 Apr;8(2):133-6.
The expressions of caspase-1 and cytokines activated by caspase-1 are associated with the pathophysiology of many diseases for its proinflammatory and proapototic peculiarity. However its relationship to brain injury of developing rats following recurrent seizures has not yet been identified. This study aimed to investigate the role of caspase-1 and cytokines activated by caspase-1 in brain injury of developing rats following recurrent seizures.
A total of 96 postnatal 20 day Sprague-Dawley rats were randomly assigned into Control and Seizure groups. Seizures were induced in the Seizure group by flurothyl inhalation daily for six days. Brain tissues were sampled at 6 hrs, and at 1, 3, and 7 days after last seizure. The expressions of caspase-1, interleukin (IL)-18 and IL-1beta mRNA in the cerebral cortex were detected by RT-PCR. The water content of the brain and the pathological changes of cortex nerve cells were observed. Brain injury was evaluated using a semiquantitative neuropathological scoring system.
The levels of caspase-1 and IL-18 mRNA in the cerebral cortex of the Seizure group were obviously higher than those in the Control group at 6 hrs, and at 1, 3, and 7 days after seizure (P < 0.05 or P < 0.01). The expression of IL-1beta mRNA in the Seizure group exhibited a biphasic pattern: increased significantly at 6 hrs, and at 1 and 7 days post-seizure (P < 0.01), but was not significantly different from the Control group at 3 days post-seizure. Edema, degeneration and necrosis of nerve cells in cerebral cortex, accompanying by inflammatory cell infiltration and apoptosis of nerve cells, were observed under a light microscope in the Seizure group after recurrent seizures. The water content of the brain in the Seizure group increased significantly compared with that in the Control group at 6 hrs, and at 1 and 3 days after recurrent seizures (P < 0.01). The Seizure group had significantly higher neuropathological scores than the Control group at each time point (P < 0.01).
Caspase-1 and cytokines activated by caspase-1 play an important role in the developing brain injury after recurrent seizures.
半胱天冬酶 -1（caspase-1）及其激活的细胞因子因其促炎和促凋亡特性，与多种疾病的病理生理学相关。然而，其与幼龄大鼠反复癫痫发作后脑损伤的关系尚未明确。本研究旨在探讨caspase-1及其激活的细胞因子在幼龄大鼠反复癫痫发作后脑损伤中的作用。
将96只出生后20天的Sprague-Dawley大鼠随机分为对照组和癫痫组。癫痫组通过每日吸入三氟乙烷诱导癫痫发作，持续6天。在末次癫痫发作后6小时、1天、3天和7天采集脑组织。采用逆转录聚合酶链反应（RT-PCR）检测大脑皮质中caspase-1、白细胞介素（IL）-18和IL-1β mRNA的表达。观察脑含水量及皮质神经细胞的病理变化。使用半定量神经病理学评分系统评估脑损伤。
癫痫组在癫痫发作后6小时、1天、3天和7天，大脑皮质中caspase-1和IL-18 mRNA水平明显高于对照组（P < 0.05或P < 0.01）。癫痫组中IL-1β mRNA的表达呈双相模式：在癫痫发作后6小时、1天和7天显著增加（P < 0.01），但在癫痫发作后3天与对照组无显著差异。反复癫痫发作后，癫痫组光镜下观察到大脑皮质神经细胞水肿、变性和坏死，伴有炎性细胞浸润和神经细胞凋亡。癫痫组在癫痫发作后6小时、1天和3天，脑含水量较对照组显著增加（P < 0.01）。癫痫组在各时间点的神经病理学评分均显著高于对照组（P < 0.01）。
caspase-1及其激活的细胞因子在反复癫痫发作后幼龄大鼠脑损伤中起重要作用。
