A Novel Mouse Model of Temporal Lobe Epilepsy

颞叶癫痫的新型小鼠模型

基本信息

批准号：
8465291
负责人：
H Steve WHITE
金额：
$ 28.85万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8465291
关键词：
AMPA Receptors Acute Address Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Astrocytes Biological Markers Biotinylation Brain Brain region C57BL/6 Mouse Cell Death Cell surface Cells Central Nervous System Infections Central Nervous System Viral Diseases Cessation of life Chronic Clinical Convulsants Cytokine Receptors Data Development Electroencephalogram Electroencephalography Electrophysiology (science)Encephalitis Encephalitis Viruses Epilepsy Epileptogenesis Exhibits Frequencies Generations Genes Glutamate Transporter Glutamates HIV Hippocampus (Brain)Human Immune Immunoblotting Incidence Infection Infection prevention Injection of therapeutic agent Interferons Interleukin-6 Interleukins Knock-out Knockout Mice Lead Light Limbic System Medial Mediating Mediator of activation protein Modeling Molecular Target Monitor Mus Neuraxis Neurons Oryctolagus cuniculus Patch-Clamp Techniques Pathologic Pathway interactions Pharmaceutical Preparations Play Predisposition Preparation Prevention Production Rattus Recurrence Risk Role Seizures Severities Signal Transduction Simplexvirus Slice Staging Status Epilepticus Surface Synapses Synaptic Transmission TMEV TNF gene Temporal Lobe Epilepsy Testing Therapeutic Tumor Necrosis Factor Receptor Tumor Necrosis Factor-alpha Viral Viral Encephalitis Virus Diseases West Nile virus astrogliosis cytokine design entorhinal cortex gene therapy genetic manipulation innovation insight interdisciplinary approach mouse model multidisciplinary neural circuit neuron loss neuronal excitability neuropathology novel novel therapeutic intervention prevent receptor expression research study therapy design uptake

项目摘要

DESCRIPTION (provided by applicant): Viral infections of the central nervous system (CNS) are associated with an increased risk for seizures, status epilepticus (SE), and the development of chronic epilepsy. We recently described a novel animal model of viral-induced epilepsy. Mice (C57BL/6) who receive intracerebral injections of Theiler's Murine Encephalomyelitis Virus (TMEV) display acute spontaneous seizures several days after infection, survive the initial infection and go on to develop spontaneous recurrent seizures. Preliminary data using C57BL/6 mice with various cytokines or cytokine receptors knocked-out have shown that these genetic manipulations can significantly alter the pathologic sequelae observed following TMEV injection of wildtype mice. Therefore, we propose to test our overall hypothesis that TMEV infection is associated with increased expression of TNF-a that contributes to increased neuronal excitability, acute seizures, neuropathology, and ultimately, epilepsy. The proposed experiments will lead to a greater understanding of the role of viral and immune contributions to acute seizures, altered neuronal and glial function, and epileptogenesis. We will use a multidisciplinary approach; including, chronic video-EEG monitoring and brain slice electrophysiology to: 1) test the hypothesis that the TNF-a pathway plays an important role in the development of chronic seizures following TMEV infection, and 2) test the hypothesis that TNF-a signaling mediates changes in synaptic and/or glial function in the hippocampus in TMEV infected mice. We anticipate that the results generated will provide a novel model in which to study the role of infection in the development of epilepsy. In addition, these experiments will provide important new insight into the role of TNF-a in cell death, synaptic transmission and epileptogenesis and set the stage for the development of novel therapeutic interventions for the prevention of infection-induced epilepsy.

描述（由申请人提供）：中枢神经系统（CNS）的病毒感染与癫痫发作、癫痫持续状态（SE）和慢性癫痫发展的风险增加相关。我们最近描述了一种病毒诱发癫痫的新型动物模型。接受泰勒氏鼠脑脊髓炎病毒（TMEV）脑内注射的小鼠（C57BL/6）在感染几天后表现出急性自发性癫痫发作，在最初的感染中存活下来，并继续发展自发性复发性癫痫发作。使用敲除各种细胞因子或细胞因子受体的 C57BL/6 小鼠的初步数据表明，这些基因操作可以显着改变野生型小鼠注射 TMEV 后观察到的病理后遗症。因此，我们建议检验我们的总体假设，即 TMEV 感染与 TNF-a 表达增加有关，从而导致神经元兴奋性增加、急性癫痫发作、神经病理学并最终导致癫痫。拟议的实验将有助于更好地了解病毒和免疫对急性癫痫发作、神经元和神经胶质功能改变以及癫痫发生的作用。我们将采用多学科方法；包括慢性视频脑电图监测和脑切片电生理学，以：1）检验 TNF-a 通路在 TMEV 感染后慢性癫痫发作的发展中发挥重要作用的假设，以及 2）检验 TNF-a 信号传导介导的假设TMEV 感染小鼠海马突触和/或神经胶质功能的变化。我们预计所产生的结果将提供一种新模型来研究感染在癫痫发展中的作用。此外，这些实验将为 TNF-a 在细胞死亡、突触传递和癫痫发生中的作用提供重要的新见解，并为开发预防感染诱发癫痫的新型治疗干预措施奠定基础。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Impaired cognitive ability and anxiety-like behavior following acute seizures in the Theiler's virus model of temporal lobe epilepsy.

DOI：
10.1016/j.nbd.2013.12.015
发表时间：
2014-04
期刊：
Neurobiology of disease
影响因子：
6.1
作者：
Umpierre AD;Remigio GJ;Dahle EJ;Bradford K;Alex AB;Smith MD;West PJ;White HS;Wilcox KS
通讯作者：
Wilcox KS

Evaluating an Etiologically Relevant Platform for Therapy Development for Temporal Lobe Epilepsy: Effects of Carbamazepine and Valproic Acid on Acute Seizures and Chronic Behavioral Comorbidities in the Theiler's Murine Encephalomyelitis Virus Mouse Model