Penetrating brain injury and copper fragments in a rat model of posttraumatic Epilepsy

项目摘要 创伤性脑损伤（TBI）是平民和军事人员的主要神经问题， 最具破坏性的结果是创伤后癫痫（PTE）。几种类型的动物模型已经 旨在复制TBI和PTE的主要特征。许多研究小组试图 使用这些啮齿动物模型来研究PTE，但我们和其他几个小组发现， 一小部分脑损伤的啮齿类动物实际上会出现真正的自发性复发性癫痫发作，这是 PTE的标志。事实上，许多回顾性研究PTE的临床报告，包括经典的工作， Annegers和同事（1998年）发现，在许多经历过这种情况的患者中， TBI实际上会发展PTE;然而，对于这些人来说，它可能会严重衰弱。中的实验 本研究计划旨在以某种方式修改这些动物模型之一，受控皮质撞击（CCI）， 使它包括一个模拟的穿透性创伤与小金属碎片，因为将发生与枪击 爆炸造成的创伤或导弹伤害。我们的初步研究强烈表明，结合CCI- 铜碎片的损伤将其从相对较少的癫痫发作次数转变为大多数癫痫发作的次数。 动物具有自发的复发性癫痫发作，并且它们以相对高的频率发生。我们提出的 实验的目的是测试一个假设，即一个与铜碎片TBI，将发生在现代枪击 创伤头部，大大增强了TBI CCI模型中的自发复发性癫痫发作。这些 研究不仅可以为TBI的哪些特征实际上构成了某些TBI的基础提供重要的新见解， 破坏性形式的PTE，但也将提供框架，为未来的修改动物模型， TBI使我们能够为自发性癫痫发作提供更好的对症治疗，并找到更好的治疗方法。 治疗以阻断创伤后癫痫的发展。

Project Summary Traumatic brain injury (TBI) is a major neurological problem for both civilians and military personnel, and one of the most devastating outcomes is posttraumatic epilepsy (PTE). Several types of animal models have been developed to attempt to replicate the major features of TBI and PTE. Many research groups have attempted to use these animal models in rodents to study PTE, but we and several other groups have found that only a small fraction of brain-injured rodents actually develop genuine spontaneous recurrent seizures, which are the hallmark of PTE. Actually, many clinical reports of retrospective studies of PTE, including the classical work of Annegers and coworkers (1998), have found only a small fraction of the many patients who have experienced TBI actually develop PTE; however, for those individuals it can be profoundly debilitating. The experiments in this research proposal aim to modify one of these animal models, controlled cortical impact (CCI), in a manner to make it include a simulation of a penetrating TBI with small metal fragments, as would occur with a gunshot wound or a missile injury from an explosion. Our preliminary studies strongly suggest that combining a CCI- injury with copper fragments converts it from one with a relatively small number of seizures to one where most animals have spontaneous recurrent seizures and they occur at a relatively high frequency. Our proposed experiments aim to test the hypothesis that a TBI with copper fragments, as would occur in a modern gunshot wound to the head, greatly enhances the spontaneous recurrent seizures in the CCI model of TBI. These studies would not only provide critical new insights into what characteristics of the TBI actually underlie some devastating forms of PTE, but would also provide the framework for future modifications of animal models of TBI to allow us to provide better symptomatic treatment of the spontaneous seizures, and to find better therapies to block the development of posttraumatic epileptogenesis.