Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.

In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed le...

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Autores principales:	Chuncheng Xie, Jiahang Sun, Weidong Qiao, Dunyue Lu, Lanlan Wei, Meng Na, Yuanyuan Song, Xiaohua Hou, Zhiguo Lin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/799e98a4465c495a8fdab2d585f0cf9e
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spelling	oai:doaj.org-article:799e98a4465c495a8fdab2d585f0cf9e2021-11-04T06:08:16ZAdministration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.1932-620310.1371/journal.pone.0024966https://doaj.org/article/799e98a4465c495a8fdab2d585f0cf9e2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21949812/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP) staining and neuron loss using Nissl staining in hippocampus at 4-6 months after KA-lesion. We found that simvastatin suppressed reactive astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar (DH). We next assessed aberrant mossy fiber sprouting (MFS) that is known to contribute to recurrence of spontaneous seizure in epileptic brain. In contrast to the robust MFS observed in saline-treated animals, the extent of MFS was restrained by simvastatin in epileptic rats. Attenuated MFS was related to decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying decreased hippocampal susceptibility in animal treated with simvastatin. Electronic encephalography (EEG) was recorded during 4 to 6 months after KA-lesion. The frequency of abnormal spikes in rats with simvastatin-treatment decreased significantly compared to the saline group. In summary, simvastatin treatment suppressed cytokines expression and reactive astrocytosis and decreased the frequency of discharges of epileptic brain, which might be due to the inhibition of MFS in DH. Our study suggests that simvastatin administration might be a possible intervention and promising strategy for preventing SE exacerbating to chronic epilepsy.Chuncheng XieJiahang SunWeidong QiaoDunyue LuLanlan WeiMeng NaYuanyuan SongXiaohua HouZhiguo LinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24966 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chuncheng Xie Jiahang Sun Weidong Qiao Dunyue Lu Lanlan Wei Meng Na Yuanyuan Song Xiaohua Hou Zhiguo Lin Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.
description	In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP) staining and neuron loss using Nissl staining in hippocampus at 4-6 months after KA-lesion. We found that simvastatin suppressed reactive astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar (DH). We next assessed aberrant mossy fiber sprouting (MFS) that is known to contribute to recurrence of spontaneous seizure in epileptic brain. In contrast to the robust MFS observed in saline-treated animals, the extent of MFS was restrained by simvastatin in epileptic rats. Attenuated MFS was related to decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying decreased hippocampal susceptibility in animal treated with simvastatin. Electronic encephalography (EEG) was recorded during 4 to 6 months after KA-lesion. The frequency of abnormal spikes in rats with simvastatin-treatment decreased significantly compared to the saline group. In summary, simvastatin treatment suppressed cytokines expression and reactive astrocytosis and decreased the frequency of discharges of epileptic brain, which might be due to the inhibition of MFS in DH. Our study suggests that simvastatin administration might be a possible intervention and promising strategy for preventing SE exacerbating to chronic epilepsy.
format	article
author	Chuncheng Xie Jiahang Sun Weidong Qiao Dunyue Lu Lanlan Wei Meng Na Yuanyuan Song Xiaohua Hou Zhiguo Lin
author_facet	Chuncheng Xie Jiahang Sun Weidong Qiao Dunyue Lu Lanlan Wei Meng Na Yuanyuan Song Xiaohua Hou Zhiguo Lin
author_sort	Chuncheng Xie
title	Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.
title_short	Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.
title_full	Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.
title_fullStr	Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.
title_full_unstemmed	Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.
title_sort	administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/799e98a4465c495a8fdab2d585f0cf9e
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Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.

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