Department of Pediatrics, Northwestern University Children's Memorial Hospital, Chicago, IL, USA.
J Neuroinflammation. 2009 Dec 19;6:38. doi: 10.1186/1742-2094-6-38.
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.
为了阐明脑炎症和细胞死亡是否存在于儿童癫痫的神经并发症和难治性癫痫中，并探讨其潜在作用，我们对接受癫痫手术的患者的脑组织进行了细胞死亡、星形胶质细胞增殖、小胶质细胞活化和细胞因子释放的定量分析。
从 13 名因局灶性皮质发育不良（6 例）、脑软化（5 例）、Rasmussen 脑炎（1 例）或内侧颞叶癫痫（1 例）导致难治性癫痫的患者中采集皮质组织。使用神经元、星形胶质细胞、小胶质细胞或细胞损伤的标志物对组织切片进行免疫组织化学处理。对冷冻皮质进行细胞因子检测。对照组为 8 例无神经病史的尸检脑。
在致痫组织中观察到小胶质细胞和星形胶质细胞的显著活化和弥漫性细胞死亡。大量纤维状星形胶质细胞及其突起覆盖整个皮质，并向血管、神经元和小胶质细胞聚集。大量神经元和星形胶质细胞显示 DNA 片段化，其程度与癫痫发作频率显著相关。我们的大多数患者在皮质中都有大量的细胞死亡，且存在智力迟钝。致痫皮质中 IL-1β、IL-8、IL-12p70 和 MIP-1β 显著增加；有癫痫家族史的患者中，IL-6 和 MCP-1 显著升高。
我们的结果表明，在儿童癫痫中存在活跃的神经炎症和明显的细胞损伤，这可能在不同病因的儿童癫痫中发挥共同的致病作用或后果。我们的发现支持这样一种观点，即针对活化的小胶质细胞和星形胶质细胞的免疫调节可能是减少神经并发症和预防难治性癫痫的一种新的治疗策略。
