Epilepsy after penetrating brain injury

脑创伤是癫痫的常见原因，尤其是穿透伤(如枪击)造成的创伤 创伤)，其中60%的受伤幸存者可能会患上癫痫。有3000多名幸存的退伍军人 在最近的穿透性脑损伤战争中，估计有11,000名新的头部创伤幸存者 美国平民每年都会患上癫痫，因此这一群体患癫痫的可能性很大。数据 还表明，严重头部损伤幸存者患痴呆症的风险增加。 已确定的继发性癫痫的危险因素之一是存在外来物质，包括 子弹上的金属碎片(如铜和铅)。目前，人们对此知之甚少。 这种类型癫痫的病理生理学以及危险因素如何在癫痫的发展中起作用 癫痫发作。铜和铅是有毒物质，长期来看有可能造成更大的损害。 学期。我们最近开发了一种穿透性脑损伤的模型，该模型的癫痫发病率高于 80%，而病变中铜的存在是关键因素，因为仅病变本身的 癫痫的发病率。除了癫痫，这些金属碎片也与显著的 动物随访6个月后出现脑坏死和脑体积丢失。这广泛地增加了 在没有添加金属的情况下，受损的动物不会受到损害。这些观察结果提出了一些 关于癫痫病因的问题，以及它们对癫痫幸存者的临床护理的影响 这些伤害，特别是如果这些金属在最初的伤害之外造成进一步的损害。在我们开始之前 进展性损伤的诸多力学问题及其发展 癫痫，我们必须关注两个基本问题，这将为所有后续研究确定方向 这可能有助于指导未来的临床护理。这个项目中的问题是1)它是不是 接触有毒金属会导致癫痫吗？和2)是与铜有关的损害程度 铅与接触金属的时间长短有关吗？这个项目的中心假设是 与残留有毒金属碎片的存在有关的损害和癫痫是由 暴露在金属中的持续时间。我们将用我们的创伤后新模型来回答这些问题 首先在大鼠身上造成穿透性损伤，在此基础上增加不锈钢(对照)、铅或 铜和评估动物癫痫的发展和损伤的严重程度 预先确定的对这两种金属的暴露。确定损害的严重程度和发展 癫痫发作受暴露时间长短的影响会对临床护理产生重大影响 降低癫痫和长期功能恶化的风险。研究结果还将为以下工作提供依据 未来对这种获得性局灶性癫痫的机制进行更深入的研究。

Brain trauma is a common cause of epilepsy, especially trauma from penetrating injuries (e.g. gun shot wounds) in which 60% of the injury survivors may develop epilepsy. There are over 3000 surviving veterans of the recent wars with penetrating brain injuries, and an estimated 11,000 new head wound survivors in the American civilian population each year, so the potential for epilepsy among this group is significant. Data also suggest that severe head injury survivors have an increased risk for the later development of dementia. One of the established risk factors for subsequent epilepsy is the presence of foreign materials, including metallic fragments (e.g. copper and lead) from bullets. At present very little is known about the pathophysiology of this form of epilepsy and how the risk factors contribute to the development of the seizures. Copper and lead are toxic materials that have the potential to cause greater damage over the long term . We have recently developed a model of penetrating brain injury that has an incidence of epilepsy over 80%, and the presence of copper in the lesion is the critical factor, as the lesion alone has a much lower incidence of epilepsy. In addition to the epilepsy, these metal fragments also are associated with significant brain necrosis and volume loss over the 6 months that the animals were followed. This extensive added damage is not seen in lesioned animals without the added metal. These observations raise a number of questions about the causes of epilepsy, and they also have implications for the clinical care of the survivors of these injuries, especially if these metals cause further damage beyond the initial injury. Before we can start to investigate the many mechanistic questions about the progressive injuries and the development of epilepsy, we have to focus on two fundamental issues which will set the direction for all subsequent studies and which may help direct future clinical care. The questions in this project are 1) Is it the duration of the exposure to the toxic metals that lead to epilepsy? and 2) Is the extent of the damage associated with copper and lead related to the duration of exposure to the metals? The central hypothesis for this project is The damage and the epilepsy related to the presence retained toxic metal fragments result from the duration of exposure to the metals. We will answer these questions with our new model of post traumatic epilepsy by first creating a penetrating injury in rats, adding to the injury stainless steel (control), lead or copper and evaluating the animals for the development of epilepsy and the severity of the injury following predetermined exposures to the two metals. Determining that the severity of damage and the development of epilepsy are influenced by the length of exposure will have a significant impact on clinical care directed to reducing the risks for epilepsy and long term functional deterioration. The results will also provide a basis for more in depth future studies on the mechanisms of this type of acquired focal epilepsy.