Inflammation induced by LPS enhances epileptogenesis in immature rat and may be partially reversed by IL1RA.

Inflammation induced by LPS enhances epileptogenesis in immature rat and may be partially reversed by IL1RA.
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DOI:
10.1111/j.1528-1167.2010.02606.x
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发表时间:
2010-07
期刊:
影响因子:
5.6
通讯作者:
Sankar R
Sankar R
中科院分区:
医学1区
文献类型:
--
作者:
Auvin S;Shin D;Mazarati A;Sankar R

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CNS中的炎症信号传导已被证明会加剧癫痫发作活动和癫痫诱导的神经元损伤。然而,它还没有确定是否神经变性是一个先决条件的促惊厥作用的神经炎症,或后者是否可能促进癫痫发作,而不涉及神经元损伤。我们研究了炎症在快速点燃模型中的作用,其中癫痫发作进展在没有神经变性的情况下发生。对P14雄性Wistar大鼠进行快速点燃程序-以已建立的诱导后放电的电流每5分钟对海马进行60次电刺激。注射LPS(50μg/kg,在RKP前2 h腹膜内);注射IL-1 Ra(25 mg/kg,在RKP前2 h腹膜内)。检查治疗对基线海马兴奋性、快速点燃进展和快速点燃保持的影响。LPS可明显增加基础海马兴奋性,表现为海马ADT的降低。LPS也增加点燃进展。点燃程序完成后24小时,与盐水处理的点燃对照相比,LPS处理的动物表现出增加的兴奋性。当IL 1 RA与LPS联合给药时,点燃进程被阻断。IL 1 RA能逆转LPS对ADD的影响,而IL 1 RA单独使用可降低ADT。我们发现,炎症引起的LPS增强快速点燃癫痫发生在未成年大鼠的大脑。IL 1 RA还能够减轻LPS增强的癫痫发生的这种增强。
Inflammatory signaling in the CNS has been shown to exacerbate both seizure activity and seizure-induced neuronal injury. However, it has not been firmly established whether neurodegeneration is a prerequisite of proconvulsant effect of neuroinflammation, or whether the latter may facilitate seizures without involving neuronal injury. We examined effects of inflammation in the rapid kindling model, where seizure progression occurs in the absence of neurodegeneration. P14 male Wistar rats were subjected to a rapid kindling procedure –60 electrical stimulations of the hippocampus delivered every five minutes at the current that had been established to induce afterdischarge. LPS was injected (50μg/kg i.p. 2h prior the RKP); IL-1Ra was injected (25mg/kg i.p. 2h prior the RKP). The effects of treatments were examined on baseline hippocampal excitability; on the progression of rapid kindling; and on the retention of rapid kindling. LPS increased baseline hippocampal excitability evident as the decrease of hippocampal ADT. LPS also increased kindling progression. 24 hrs after the completion of kindling procedure, LPS treated animals exhibited increased excitability as compared with saline-treated kindling controls. The kindling progression was blocked by IL1RA when given combination with LPS. IL1RA was able to reverse the effect of LPS on ADD while IL1RA alone decrease ADT. We showed that inflammation provoked by LPS enhanced rapid kindling epileptogenesis in immature rat brains. IL1RA was also able to mitigate this augmentation of epileptogenesis enhanced by LPS.
DOI: 10.1111/j.1528-1167.2008.01674.x
发表时间: 2008-10-01
期刊: EPILEPSIA
影响因子: 5.6
作者:
Mazarati, Andrey;Wu, Jim;Sankar, Raman
通讯作者: Sankar, Raman
DOI: 10.1016/j.nbd.2008.05.007
发表时间: 2008-09-01
影响因子: 6.1
作者:
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通讯作者: Vezzani, Annamaria
DOI: 10.1159/000026433
发表时间: 2000-01-01
影响因子: 2.4
作者:
Hu, SX;Sheng, WS;Chao, SC
通讯作者: Chao, SC
DOI: 10.1111/j.0013-9580.2004.13704.x
发表时间: 2004-11-01
期刊: EPILEPSIA
影响因子: 5.6
作者:
Heida, JG;Boiss, L;Pittman, QJ
通讯作者: Pittman, QJ
DOI: 10.1016/0165-3806(91)90116-z
发表时间: 1991-07-16
期刊: DEVELOPMENTAL BRAIN RESEARCH
影响因子: --
作者:
MICHELSON, HB;LOTHMAN, EW
通讯作者: LOTHMAN, EW