Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development
Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development
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DOI：
10.1016/j.nbd.2003.08.001
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发表时间：
2003-12-01
影响因子：
6.1
通讯作者：
Vezzani, A
中科院分区：
文献类型：
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作者：
Rizzi, M;Perego, C;Vezzani, A
在成年大鼠中，癫痫持续状态（SE）诱导神经胶质细胞产生细胞因子，特别是当癫痫发作与神经元损伤相关时。这表明细胞因子可能在癫痫引起的神经元损伤中起作用。由于se诱导的损伤具有年龄特异性，我们使用不同年龄的大鼠（对癫痫诱导的神经元损伤的易感性不同）来阐明细胞因子在这一过程中的作用。因此，我们在出生后第9,15和21天（PN）的大鼠中研究了小胶质细胞和星形胶质细胞的激活，细胞因子的诱导和海马神经元损伤。在PN9，小胶质细胞和星形胶质细胞在研究的任何时间点几乎没有活化。白细胞介素-1 β (IL)、肿瘤坏死因子- α (TNF)、IL-6或自然产生的IL-1受体拮抗剂（Ra） mRNA的表达没有增加。没有发现细胞损伤的证据。在PN15时，小胶质细胞和星形胶质细胞的免疫染色增强，但只有il -1 β mRNA表达增加。这些变化在SE后4小时观察到。SE后24 h， CA3和耻骨下有分散的损伤神经元，其他区域未见损伤。在PN21时，SE后4 h小胶质细胞和星形胶质细胞的免疫染色和所研究的所有细胞因子的mRNA表达均已显著升高。24 h时，在CA1和CA3区以及40%的大鼠的其他前脑区存在许多损伤的神经元。这些数据表明：(1)SE诱导的胶质细胞激活和细胞因子基因转录模式是年龄依赖性的；(2)海马神经元损伤仅在细胞因子被诱导且其合成先于神经元损伤出现时发生。因此，未成熟大脑中的细胞因子表达与细胞损伤特异性相关，而不是与癫痫发作本身相关，这表明促炎细胞因子可能有助于se诱导的海马损伤的发生。(C) 2003 Elsevier Inc.版权所有。
In adult rats, status epilepticus (SE) induces cytokine production by glia especially when seizures are associated with neuronal injury. This suggests that cytokines may play a role in seizure-induced neuronal damage. As SE-induced injury is age-specific, we used rats of different ages (with distinct susceptibilities to seizure-induced neuronal injury) to elucidate the role of cytokines in this process. Thus, we investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal injury 4 and 24 h following kainic acid-induced SE in postnatal day (PN) 9, 15, and 21 rats. At PN9, there was little activation of microglia and astrocytes at any time point studied. Interleukin-1beta (IL), tumor necrosis factor-alpha (TNF), and IL-6 or the naturally occurring IL-1 receptor antagonist (Ra) mRNA expression did not increase. No evidence of cell injury has been detected. At PN15, immunostaining of microglia and astrocytes was enhanced, but only IL-1beta mRNA expression was increased. These changes were observed 4 h after SE. Scattered injured neurons in CA3 and subiculum, but not in any other region, were present 24 h following SE. At PN21, immunostaining of microglia and astrocytes and the mRNA expression of all cytokines studied was significantly increased already 4 h after SE. At 24 h, many injured neurons were present in CA1 and CA3 regions and in 40% of rats in other forebrain areas. These data show that (i) the pattern of glia activation and cytokine gene transcription induced by SE is age-dependent and (ii) neuronal injury in the hippocampus occurs only when cytokines are induced and their synthesis precedes the appearance of neuronal damage. Thus, cytokine expression in immature brain is associated specifically with cell injury rather than with seizures per se, suggesting that proinflammatory cytokines may contribute to the occurence of SE-induced hippocampal damage. (C) 2003 Elsevier Inc. All rights reserved.