Cellular injury and neuroinflammation in children with chronic intractable epilepsy.
Cellular injury and neuroinflammation in children with chronic intractable epilepsy.
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DOI：
10.1186/1742-2094-6-38
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发表时间：
2009-12-19
影响因子：
9.3
通讯作者：
Koh S
中科院分区：
文献类型：
--
作者：
Choi J;Nordli DR Jr;Alden TD;DiPatri A Jr;Laux L;Kelley K;Rosenow J;Schuele SU;Rajaram V;Koh S
为了阐明脑部炎症和细胞死亡在儿童癫痫的神经系统疾病和难治性癫痫发作中的存在和潜在参与，我们对接受癫痫手术的患者脑组织中的细胞死亡、星形胶质细胞增殖、小胶质细胞激活和细胞因子释放进行了量化。13例因局灶性皮质发育不良(6例)、脑软化症(5例)、拉斯穆森脑炎(1例)或内侧颞叶癫痫(1例)所致的顽固性癫痫患者的大脑皮质组织。切片用神经元、星形胶质细胞、小胶质细胞或细胞损伤标志物进行免疫组织化学处理。对冰冻皮质进行细胞因子检测。对照组是来自8名无神经系统疾病病史的患者的尸检大脑。致痫组织小胶质细胞和星形胶质细胞明显激活，弥漫性细胞死亡。大量的纤维状星形胶质细胞及其突起覆盖整个皮质，并汇聚到血管、神经元和小胶质细胞。绝大多数神经元和星形胶质细胞显示DNA片段化，其大小与癫痫发作频率显著相关。我们的大多数大脑皮层有大量细胞死亡的患者都有智力低下。致痫皮质区IL-1β、IL-8、IL-12p70和MIP-1显著升高，有癫痫家族史者IL-6和MCP-1显著升高。我们的结果表明，活跃的神经炎症和明显的细胞损伤发生在儿童癫痫中，并可能在不同原因的儿童癫痫中起到共同的致病作用或后果。我们的发现支持以激活的小胶质细胞和星形胶质细胞为靶点的免疫调节可能是降低神经系统发病率和预防难治性癫痫的一种新的治疗策略。
To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery. Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases. Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy. Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.
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影响因子：
1.9
作者：
Haspolat, S;Mihçi, E;Yegin, O
通讯作者：
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