Seizure duration following sarin exposure affects neuro-inflammatory markers in the rat brain
Seizure duration following sarin exposure affects neuro-inflammatory markers in the rat brain
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DOI：
10.1016/j.neuro.2005.11.009
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发表时间：
2006-03-01
期刊：
影响因子：
3.4
通讯作者：
Gilat, E
中科院分区：
文献类型：
--
作者：
Chapman, S;Kadar, T;Gilat, E
本研究的目的是首次描述沙林44暴露在大鼠脑内引发的神经炎性标志物的变化，并探讨其与癫痫发作持续时间的相关性。中枢介导的癫痫发作，是暴露于有机磷(OP)的常见后果，尽管传统的治疗方法是阿托品和肟类药物。在本研究中，咪达唑仑用于控制癫痫发作的持续时间和强度。用咪达唑仑治疗大鼠癫痫发作5分钟或30分钟后，观察沙林暴露后不同时间海马区和皮质区促炎症细胞因子IL-1β、IL-6、肿瘤坏死因子-α和前列腺素E-2(PGE(2))水平的变化。脑组织生化检测显示，在沙林中毒后2小时，促炎性多肽水平显著升高，2-24小时达到峰值。海马区IL1-β含量从对照组的1.2+/-0.1pg/mg组织增加到2 h(5 min 9次惊厥)的2.4+/-0.3和8 h(30 Min)的9.3+/-2.5。惊厥后5min和30min，大鼠海马区PGE(2)水平分别从暴露前的56+/-3升至175+/-26和277+/-28pg/mg组织，持续至24 h。因此。与咪达唑仑将癫痫发作限制在5min不同，延迟治疗(30min)可延长癫痫发作时间，并显著增加细胞因子和PGE(2)。此外。在沙林暴露30天后，只有在30分钟的癫痫发作活动后，才观察到第二次炎性标志物的增加。本研究对大鼠大脑的组织学评估显示，在沙林诱导的癫痫发作活动5分钟后，少数动物的海马区和梨状皮质没有损伤，仅有少量动物侧脑室扩大。相比之下，癫痫发作30分钟后，脑组织发生了明显的损伤，包括海马体、梨状皮质和一些丘脑核团的严重损伤。综上所述，提出了伴随沙林暴露而延长的中枢神经炎症过程的新特征。抗惊厥治疗的时机被证明是调节神经炎性反应的关键，并可能导致随后的长期脑损伤。(C)2005 Elsevier Inc.保留所有权利。
The current study was aimed to characterize for the first time the alterations in the characteristic neuro-infiammatory markers triggered by sarin 44 exposure in the rat's brain, and to investigate its dependency on seizure duration. Centrally mediated seizure, are a common consequence of exposure to organophosphates (OP) despite conventional treatment with atropine and an oxime. In the present study midazolam, was used to control duration and intensity of seizures. The levels of the pro-inflammatory cytokine peptides IL-1 beta IL-6, TNF-alpha and prostaglandin E-2 (PGE(2)) were monitored at various times after sarin exposure in the hippocampus and cortex of rats treated with midazolam following 5 or 30 min of seizure activity. Biochemical evaluation of brain tissues revealed a significant increase in the level of the pro-inflammatory peptides starting at 2 h and peakin at 2-24 h following sarin. Hippocampal values of IL1-beta increased from 1.2 +/- 0.1 pg/mg tissue (control), to 2.4 +/- 0.3 at 2 h (5 min 9 seizure) and to 9.3 +/- 2.5 at 8 h (30 min seizure). PGE(2) level in the hippocampus increased up to 24 h following exposure (from 56 +/- 3 to 175 +/- 26 and 277 +/- 28 pg/mg tissue) following 5 and 30 min of seizure activity respectively. Thus. unlike limitation of seizures to 5 min by midazolam, delayed treatment (30 min) resulted in prolonged seizures and pronounced increase in cytokines and PGE(2). In addition. a second increase in inflammatory markers was observed 30 days following sarin exposure only in rats treated following 30 min of seizure activity.Histological evaluation of the rat brain, conducted in this study, revealed lack of damage in the hippocampus and piriform cortex with minor lateral ventricles enlargement in few animals following 5 min of sarin-induced seizure activity. In contrast, marked histological damage to the brain was demonstrated following 30 min of seizure activity, consisting severe damage to the hippocampus, piriform cortex and some thalamic nuclei. In summary, a novel characterization of the prolonged central neuro-inflammatory process that accompanies sarin exposure is presented. The timing of the anticonvulsive treatment was shown to be crucial in modulation of the neuro-inflammatory response, and may implicate the consequent long-term brain damage. (c) 2005 Elsevier Inc. All rights reserved.