Automated quantification of EEG spikes and spike clusters as a new read out in Theiler's virus mouse model of encephalitis-induced epilepsy

被引:30
作者
Anjum, Syed Muhammad Muneeb [1 ,2 ]
Kaeufer, Christopher [1 ]
Hopfengaertner, Ruediger [3 ]
Waltl, Inken [1 ,2 ]
Broeer, Sonja [1 ,4 ]
Loescher, Wolfgang [1 ,2 ]
机构
[1] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Bunteweg 17, D-30559 Hannover, Germany
[2] Ctr Syst Neurosci, Hannover, Germany
[3] Univ Hosp Erlangen, Dept Neurol, Epilepsy Ctr, Erlangen, Germany
[4] Neuron Therapeut, San Francisco, CA USA
关键词
Seizures; TMEV; Epileptogenesis; Neuroinflammation; Hippocampal damage; TEMPORAL-LOBE EPILEPSY; MURINE ENCEPHALOMYELITIS VIRUS; PICORNAVIRUS INFECTION; INTERICTAL SPIKES; MULTIPLE-SCLEROSIS; STATUS EPILEPTICUS; BRAIN; SEIZURES; MICE; EPILEPTOGENESIS;
D O I
10.1016/j.yebeh.2018.09.016
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Intracerebral infection of C57BL/6 mice with Theiler's murine encephalomyelitis virus (TMEV) replicates many features of viral encephalitis-induced epilepsy in humans, including neuroinflammalion, early (insult-associated) and late (spontaneous) seizures, neurodegeneration in the hippocampus, and cognitive and behavioral alterations. Thus, this model may be ideally suited to study mechanisms involved in encephalitis-induced epilepsy as potential targets for epilepsy prevention. However, spontaneous recurrent seizures (SRS) occur too infrequently to be useful as a biomarker of epilepsy, e.g., for drug studies. This prompted us to evaluate whether epileptiform spikes or spike clusters in the cortical electroencephalogram (EEG) may be a useful surrogate of epilepsy in this model. For this purpose, we developed an algorithm that allows efficient and large-scale EEG analysis of early and late seizures, spikes, and spike clusters in the EEG. While 77% of the infected mice exhibited early seizures, late seizures were only observed in 33% of the animals. The clinical characteristics of early and late seizures did not differ except that late generalized convulsive (stage 5) seizures were significantly longer than early stage 5 seizures. Furthermore, the frequency of SRS was much lower than the frequency of early seizures. Continuous (24/7) video-EEG monitoring over several months following infection indicated that the latent period to onset of SRS was 61 (range 16-91) days. Spike and spike clusters were significantly more frequent in infected mice with late seizures than in infected mice without seizures or in mock-infected sham controls. Based on the results of this study, increases in EEG spikes and spike dusters in groups of infected mice may be used as a new readout for studies on antiepileptogenic or disease-modifying drug effects in this model, because the significant increase in average spike counts in mice with late seizures obviously indicates a proepileptogenic alteration. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:189 / 204
页数:16
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