HIPPOCAMPAL PLASTICITY IN EPILEPSY

癫痫中的海马可塑性

基本信息

批准号：
6330434
负责人：
THOMAS PETER SUTULA
金额：
$ 27.45万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-12-21 至 2003-11-30
项目状态：
已结题

项目摘要

Temporal lobe epilepsy is a common form of epilepsy that frequently becomes resistant to anticonvulsant drugs and is sometimes progressive. The evolving physiological and neuropathological processes that eventually made chronic susceptibility to recurring seizures, development of anticonvulsant drug resistance, and progression to intractable temporal lobe epilepsy are not well understood are not well understand. Limbic kindling has been studied as a model of temporal lobe epilepsy because kindled seizures have many features that resemble human partial complex seizures arising from the temporal lobe. Repeated brief seizures evoked by kindling, which gradually increase susceptibility to additional seizures and eventually induce spontaneous seizures in the absence of an initial participating injury, provide an opportunity to study how repeated seizures may contribute to intractable temporal lobe epilepsy. In the dentate gyrus, kindling induces neuronal loss and mossy fiber sprouting, which are also observed in the human epileptic temporal lobe. Seizure- induced cellular alterations such as neuronal loss and formation of recurrent circuits formed by sprouted mossy fibers could increase susceptibility to additional seizures by modifying the balance of excitation and inhibition of hippocampal pathways. Recent studies in our lab have revealed that the development of spontaneous seizures during kindling coincides with loss of inhibition in the dentate gyrus. The proposed experiments. utilize anatomical and physiological methods to investigate the relationship between repeated seizures, reduction of inhibition, and chronic seizure-induced cellular alterations in the dentate gyrus that contribute to spontaneous seizures and intractable epilepsy. The results of these studies will be important for understanding how poorly controlled seizures in people may contribute to recurring seizures and intractable temporal lobe epilepsy.

颞叶癫痫是一种常见的癫痫的形式，经常对抗惊厥药具有抵抗力，有时是进行性疾病。最终使重复癫痫发作的长期敏感性，抗药性耐药性的发展以及发展为棘手的颞叶癫痫的发展尚不很好地理解的生理和神经病理学过程不太了解。边缘点燃已被研究为颞叶癫痫的模型，因为点燃的癫痫发作具有许多类似于颞叶引起的人类部分复合物癫痫发作的特征。点燃引起的重复短暂癫痫发作逐渐增加了对额外癫痫发作的敏感性，并最终在没有初始参与损伤的情况下诱导自发癫痫发作，这提供了一个机会，可以研究重复癫痫发作如何导致棘手的颞叶癫痫病。在齿状回中，点燃会诱导神经元丧失和苔藓纤维发芽，在人类癫痫性颞叶中也观察到。癫痫发作诱导的细胞改变，例如神经元丧失和由发芽的苔藓纤维形成的复发电路的形成，可以通过修改兴奋平衡和海马途径的抑制来增加对额外癫痫发作的敏感性。我们实验室中的最新研究表明，在点燃过程中，自发癫痫发作的发展与齿状回的抑制作用丧失相吻合。提出的实验。利用解剖学和生理方法来研究反复癫痫发作，抑制减少以及慢性癫痫发作诱导的齿状回的细胞改变，这有助于自发性癫痫发作和顽固性癫痫。这些研究的结果对于理解人们控制率较差的人的癫痫发作可能有助于反复出现的癫痫发作和棘手的颞叶癫痫。