权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Epileptogenic effects of periventricular nodular heterotopia

脑室周围结节性异位的致癫痫作用

基本信息

批准号：
8051831
负责人：
PHILIP A SCHWARTZKROIN
金额：
$ 32.59万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2013-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Epilepsies are often associated with abnormalities in brain structure. These abnormalities take many different forms, and can be a consequence of gene mutations, perinatal insults, or brain trauma. The aberrant structures collectively sometimes referred to as cortical dysplasias frequently reflect developmental brain defects. We propose to study an animal model of one type of cortical dysplasia, called periventricular nodular heterotopia (PNH). This condition is most frequently a result of a gene mutation that interferes with normal migration of newborn cells into their proper location in the cortex. Most people with this condition suffer from a seizure disorder, often unresponsive to medication. Some clinical studies have suggested these heterotopias serve as initiation sites of epileptic discharge and/or seizures, but these studies have been unable to establish an unequivocal cause-effect relationship between structural and functional abnormalities. Our goal in the current proposal is to gain insight into how and where PNH-associated seizures develop. We plan to study a rat model of PNH induced by treating the pregnant dam with methylazoxymethanol (MAM). We will use electrical recording and neuropathological techniques to assess tissue excitability and the functional integrity of the PNH structure and surrounding (and apparently normal) cortex. These procedures will be applied in the intact animal, in acute brain slices, and in organotypic cultures, in order to evaluate both the general circuitry function in cortex containing a PNH-like lesion, and also the properties of individual neurons both within and outside the PNH. In the organotypic slice preparation, we will examine the consequences of removing the PNH (e.g., as a neurosurgeon might do to treat the condition in human brain), in order to assess the efficacy of such manipulations as a function of brain development. PUBLCI HEALTH RELEVANCE: The occurrence of developmentally-based abnormalities in brain structure (e.g., periventricular nodular heterotopia) is commonly associated with seizure disorders i.e., epilepsy and other cognitive deficits. Because we understand relatively little about how this type of structural abnormality gives rise to epilepsy, our ability to treat the epilepsy effectively is limited. The aim of this proposal is to gain an understanding of the causal relationship between the structural aspects of these disorders and seizures, and to assess the efficacy of surgical removal (at different times during brain development) as a means of therapy.

描述(由申请人提供)：癫痫通常与大脑结构的异常有关。这些异常有许多不同的形式，可能是基因突变、围产期侮辱或脑损伤的结果。这些异常结构有时统称为皮质发育不良，通常反映出发育中的大脑缺陷。我们建议研究一种类型的皮质发育不良的动物模型，称为脑室周围结节异位(PNH)。这种情况最常见的是基因突变的结果，该基因突变干扰了新生细胞正常迁移到它们在皮质中的适当位置。大多数有这种情况的人都患有癫痫障碍，通常对药物没有反应。一些临床研究表明，这些异位是癫痫放电和/或癫痫发作的起始点，但这些研究一直无法在结构和功能异常之间建立明确的因果关系。我们在目前的提案中的目标是深入了解PNH相关癫痫发作是如何以及在哪里发生的。我们计划研究一种用甲氧基甲醇(MAM)治疗妊娠母鼠所致的PNH大鼠模型。我们将使用电记录和神经病理学技术来评估组织兴奋性和PNH结构及其周围(和明显正常的)皮质的功能完整性。这些程序将应用于完整的动物、急性脑片和器官培养，以评估包含PNH样病变的皮质的一般回路功能，以及PNH内外的单个神经元的特性。在器官类型切片准备中，我们将检查移除PNH的后果(例如，就像神经外科医生可能对人脑疾病所做的那样)，以评估这种操作作为大脑发育功能的有效性。PUBLCI健康相关性：脑结构发育异常(例如，脑室周围结节异位)的发生通常与癫痫和其他认知缺陷等癫痫障碍有关。由于我们对这种结构异常如何引起癫痫的了解相对较少，因此我们有效治疗癫痫的能力是有限的。这项建议的目的是了解这些疾病的结构方面与癫痫发作之间的因果关系，并评估手术切除(在大脑发育的不同时期)作为一种治疗手段的有效性。