Targeting the ventral hippocampus for a better model of temporal lobe epilepsy

针对腹侧海马以获得更好的颞叶癫痫模型

• 批准号: 9346119
• 负责人: Esther Krook-Magnuson
• 金额: $ 7.65万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9346119
• 关键词: Acute; Anterior; Antiepileptic Agents; Behavior; Behavioral; Carbamazepine; Cells; Cessation of life; Chronic; Development; Diagnosis; Disease; Dorsal; Epilepsy; Frequencies; Genetic; Genetic Predisposition to Disease; Genetic screening method; Hippocampus (Brain); Human; Human Characteristics; Injection of therapeutic agent; Intervention; Investigation; Location; Modeling; Morphology; Motor Seizures; Mouse Strains; Mus; Nature; Patients; Phenytoin; Predisposition; Property; Protocols documentation; Research; Research Personnel; Resistance; Rodent; Rodent Model; Sclerosis; Seizures; Site; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Time; data acquisition; granule cell; hippocampal sclerosis; improved; kainate; mortality; mossy fiber; mouse model; novel; public health relevance; tool

PROJECT SUMMARY/ABSTRACT The primary objective of this proposal is to produce a much needed tool for epilepsy research – a model of temporal lobe epilepsy with the strengths of the currently widely used intrahippocampal kainate model but also displaying spontaneous, overtly behavioral seizures, at a high enough frequency to allow scientific investigation. To do this, we propose a simple change to the current induction protocol, with the possibility for a huge impact. Specifically, despite known differences in connectivity and functional properties between dorsal and ventral hippocampus, and the observation that in human patients the anterior hippocampus (corresponding to the ventral hippocampus in rodents) is most likely to show hippocampal sclerosis, in its current form, the intrahippocampal kainate model targets the dorsal (rather than ventral) hippocampus. We hypothesize that better aligning the model to the human condition, by moving the site of initial insult to the ventral hippocampus, will additionally result in a substantially higher frequency of overtly behavioral seizures. This is critically important, as it would provide the field with a much needed tool, allowing investigation of more severe seizures and identification of novel treatment approaches with sufficient statistical power and feasible time frames for data acquisition.

项目总结/摘要 该提案的主要目标是生产癫痫研究急需的工具--一个 颞叶癫痫模型与目前广泛使用的海马内红藻氨酸模型的优势 而且还表现出自发的，明显的行为癫痫发作，频率足够高， 调查为了做到这一点，我们建议对目前的诱导方案进行简单的修改， 巨大的影响。具体地说，尽管背侧和背侧之间的连接性和功能特性存在已知的差异， 和腹侧海马，并观察到在人类患者中， （对应于啮齿动物的腹侧海马）最有可能显示海马硬化， 目前的形式，海马内红藻氨酸模型靶向背侧（而不是腹侧）海马。我们 假设通过将初始损伤部位移动到 腹侧海马，将另外导致明显更高频率的明显行为癫痫发作。 这一点至关重要，因为它将为实地提供一个急需的工具，使人们能够调查更多的 重度癫痫发作和识别具有足够统计功效和可行性的新型治疗方法 数据采集的时间框架。