Abstract:
PURPOSE:Our objective was to propose a new on demand non-human primate model of mesial temporal lobe seizures suitable for pre-clinical innovative therapeutic research. METHODS:Five macaques were stereotaxically implanted unilaterally with a deep recording electrode in the hippocampus. For each experiment, penicillin was injected into the hippocampus and animals were monitored during five consecutive hours. A total of 12-27 experiments with a mean cumulative dose of 162644 ± 70190 UI of penicillin have been performed per animal Injections were repeated at least once a week over a period of 98-276 days. The time-course of electro-clinical seizures and the response to diazepam have been quantified from, respectively, 84 and 11 experiments randomly selected. To evaluate brain injury produced by several penicillin injections and to characterize the changes occurring into the hippocampus, we performed an histological analysis, including neuronal nuclei and glial fibrillary acid protein immunostaining and electron microscopy. RESULTS:After each penicillin injection, we observed that the electro-clinical characteristics were reproducible among non-human primates and experiments. Seizures duration was stable (29.60 ± 6.62 s) and the frequency of seizures reached a plateau with about 3 seizures/20 min during 180 min and that could be useful to test new treatments. Diazepam did not modify the course of the seizures. Hippocampal sclerosis was found similar to that encountered in epileptic patients with a neuronal loss and a glial cells proliferation. Electron microscopy analysis of CA1 revealed a decreased number of synapses and a large amount of glial fibrillary filaments in the injected hippocampus. Interestingly, this on-demand model of seizure, turned into a chronic model with spontaneous occurrence of seizures after a cumulative amount ranging from 119 to 145 KIU of penicillin injected. CONCLUSION:The present study shows that an on-demand model of mesial temporal lobe seizure can be developed by intra-hippocampal injection of penicillin. The seizures are reproducible, stable and resistant to diazepam. Brain damages are confined to the hippocampus with similar features to that found in human mesial temporal lobe epilepsy. This model reproduces the symptomatogenic and the irritative zone usually seen in human MTLE, with the additional advantage of having a clear delineation of the epileptogenic zone. However, the mechanism of actions of the penicillin as a proconvulsant agent does not replicate all of the much more complex physiological and cellular mechanisms that are involved in human epilepsy and represent a limitation of our study that one must be aware of.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Sherdil A,Chabardès S,Guillemain I,Michallat S,Prabhu S,Pernet-Gallay K,David O,Piallat Bdoi
10.1016/j.eplepsyres.2018.03.008subject
Has Abstractpub_date
2018-05-01 00:00:00pages
20-28eissn
0920-1211issn
1872-6844pii
S0920-1211(17)30484-9journal_volume
142pub_type
杂志文章abstract::The aim of the study was to compare subjective complaints of epilepsy patients with objective results of neuropsychological assessment and to investigate the possible influence of depression on self-reported complaints. 62 patients from the neurology clinic were included in the study. They were asked to fill the subje...
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journal_title:Epilepsy research
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journal_title:Epilepsy research
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.01.008
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.05.001
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journal_title:Epilepsy research
pub_type: 杂志文章
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2008.07.011
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pub_type: 杂志文章,多中心研究
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更新日期:2017-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0920-1211(91)90069-r
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2007.05.004
更新日期:2007-07-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.09.009
更新日期:2013-03-01 00:00:00
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journal_title:Epilepsy research
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1990-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.04.002
更新日期:2006-08-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2016.09.011
更新日期:2016-11-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2008.11.015
更新日期:2009-03-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.02.011
更新日期:2018-07-01 00:00:00
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pub_type: 杂志文章
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.05.010
更新日期:2006-08-01 00:00:00
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pub_type: 杂志文章
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