Epilepsy after penetrating brain injury
脑穿透伤后癫痫
基本信息
- 批准号:10809468
- 负责人:
- 金额:$ 44.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAffectAmericanAnimalsBrainBrain InjuriesChronicClinicalConsensusCopperCraniocerebral TraumaDataDementiaDeteriorationDevelopmentEarly treatmentEpilepsyEpileptogenesisEvolutionExcisionExposure toFunctional disorderFutureGunshot woundHeadIncidenceInjuryInvestigationLeadLengthLesionMetabolicMetal exposureMetalsMilitary PersonnelModelingNatureNecrosisNeurological outcomeOutcomePartial EpilepsiesPenetrating Brain InjuryPenetrationPersonsPopulationPost-Traumatic EpilepsyProcessPrognosisRattusReportingRiskRisk FactorsRisk ReductionRoleSeizuresSeveritiesShotgunsStainless SteelSurvivorsTestingTimeTissuesTraumaTraumatic Brain InjuryVeteransWarWorkacquired epilepsyclinical careclinical practiceclinically relevantcomparison controlfunctional outcomeshigh riskimprovedimproved outcomemetallicitynovel therapeutic interventionpreventsevere injurytoxic metaltranslational potentialwound
项目摘要
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,尤其是穿透性损伤(如枪击
其中60%的受伤幸存者可能会患上癫痫。有超过3000名幸存的退伍军人
在最近的战争中,脑穿透伤,估计有11,000名新的头部受伤幸存者,
美国平民人口每年,所以癫痫的潜在这一群体是显着的。数据
这也表明,严重的头部损伤幸存者有增加的风险,为以后的发展痴呆症。
继发性癫痫的既定风险因素之一是异物的存在,包括
子弹的金属碎片(如铜和铅)。目前,人们对它知之甚少。
这种形式的癫痫的病理生理学以及风险因素如何促进癫痫的发展。
癫痫发作。铜和铅是有毒物质,长期使用有可能造成更大的损害。
term .我们最近开发了一种穿透性脑损伤模型,其癫痫发生率超过
80%,并且病变中铜的存在是关键因素,因为单独病变具有低得多的
癫痫的发病率。除了癫痫,这些金属碎片也与重要的
脑坏死和体积损失超过6个月的动物被跟踪。这一广泛的补充
在没有添加金属的损伤动物中没有观察到损伤。这些意见提出了一些
关于癫痫的原因的问题,他们也有影响的幸存者的临床护理,
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伤害。在我们开始之前
探讨了进行性损伤和发展的许多机制问题,
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。在这个项目中的问题是1)它是持续时间的
接触有毒金属会导致癫痫吗和2)与铜相关的损害程度
和铅含量与接触金属的时间有关吗这个项目的核心假设是
与残留的有毒金属碎片有关的损伤和癫痫是由
暴露于金属的时间。我们将用创伤后心理学的新模型来回答这些问题。
通过首先在大鼠中造成穿透性损伤,在损伤中加入不锈钢(对照)、铅或
铜和评估动物癫痫的发展和损伤的严重程度,
两种金属的预定暴露。确定损害的严重程度和
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退化的风险。研究结果还将为以下方面提供依据:
希望今后对这类获得性局灶性癫痫的发病机制进行更深入的研究。
项目成果
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{{ truncateString('EDWARD H BERTRAM', 18)}}的其他基金
Thalamic infusions as a treatment of limbic epilepsy
丘脑输注治疗边缘叶癫痫
- 批准号:
7821361 - 财政年份:2009
- 资助金额:
$ 44.41万 - 项目类别:
Pharmacoresistant limbic epilepsy: model validation
耐药边缘癫痫:模型验证
- 批准号:
6831039 - 财政年份:2004
- 资助金额:
$ 44.41万 - 项目类别:
Pharmacoresistant limbic epilepsy: model validation
耐药边缘癫痫:模型验证
- 批准号:
6931487 - 财政年份:2004
- 资助金额:
$ 44.41万 - 项目类别:
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