Epilepsy after penetrating brain injury

脑穿透伤后癫痫

• 批准号: 10809468
• 负责人: EDWARD H BERTRAM
• 金额: $ 44.41万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10809468
• 关键词: Address; Affect; American; Animals; Brain; Brain Injuries; Chronic; Clinical; Consensus; Copper; Craniocerebral Trauma; Data; Dementia; Deterioration; Development; Early treatment; Epilepsy; Epileptogenesis; Evolution; Excision; Exposure to; Functional disorder; Future; Gunshot wound; Head; Incidence; Injury; Investigation; Lead; Length; Lesion; Metabolic; Metal exposure; Metals; Military Personnel; Modeling; Nature; Necrosis; Neurological outcome; Outcome; Partial Epilepsies; Penetrating Brain Injury; Penetration; Persons; Population; Post-Traumatic Epilepsy; Process; Prognosis; Rattus; Reporting; Risk; Risk Factors; Risk Reduction; Role; Seizures; Severities; Shotguns; Stainless Steel; Survivors; Testing; Time; Tissues; Trauma; Traumatic Brain Injury; Veterans; War; Work; acquired epilepsy; clinical care; clinical practice; clinically relevant; comparison control; functional outcomes; high risk; improved; improved outcome; metallicity; novel therapeutic intervention; prevent; severe injury; toxic metal; translational potential; wound

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.

脑外伤是癫痫的常见原因，尤其是穿透伤（例如枪伤）造成的外伤 伤口），其中 60% 的受伤幸存者可能会患上癫痫。尚存老兵3000余人 最近的战争中出现了穿透性脑损伤，据估计，该地区新增了 11,000 名头部受伤幸存者 美国平民人口每年增加，因此这一群体患癫痫的可能性很大。数据 还表明，严重头部受伤的幸存者日后患痴呆症的风险增加。 继发癫痫的既定危险因素之一是异物的存在，包括 子弹中的金属碎片（例如铜和铅）。目前人们对此知之甚少 这种形式癫痫的病理生理学以及危险因素如何促进癫痫的发展 癫痫发作。铜和铅是有毒物质，长期存在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模型，其癫痫发病率超过 80%，病灶中铜的存在是关键因素，因为仅病灶的铜含量要低得多 癫痫的发病率。除了癫痫之外，这些金属碎片还与重大疾病有关。 跟踪动物的 6 个月内出现脑坏死和体积减少。这个广泛的补充 在不添加金属的情况下，受损动物不会受到损害。这些观察结果提出了一些 有关癫痫病因的问题，它们也对癫痫幸存者的临床护理产生影响 这些伤害，特别是如果这些金属造成超出最初伤害的进一步伤害。在我们开始之前 研究有关进行性损伤和发展的许多机制问题 对于癫痫，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。该项目中的问题是 1) 的持续时间是否是 接触有毒金属会导致癫痫吗？ 2) 与铜相关的损坏程度 铅与接触金属的时间长短有关？该项目的中心假设是 与残留有毒金属碎片有关的损伤和癫痫是由 暴露于金属的持续时间。我们将用我们的新创伤后模型来回答这些问题 首先对大鼠造成穿透性损伤，然后在损伤上添加不锈钢（对照）、铅或 铜并评估动物癫痫的发展以及随后受伤的严重程度 预先确定的两种金属暴露量。确定损害的严重程度和发展 癫痫受暴露时间长短的影响将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。研究结果也将为 未来对此类获得性局灶性癫痫的机制进行更深入的研究。