Effects of Methamphetamine in Traumatic Brain Injury

描述（由申请人提供）：甲基苯丙胺（METH）是一种高度成瘾的滥用药物，在这个国家和世界各地越来越受欢迎。冰毒是夏威夷的首选毒品，被认为是迄今为止最重大的毒品威胁。药物滥用增加了冒险行为，因此许多创伤性脑损伤（TBI）的受害者也在使用非法药物。创伤性脑损伤也是美国和世界各地的一个重要的公共卫生问题，美国每年有150万例TBI病例。METH和TBI均可单独引起神经元的直接毒性，并改变脑灌注。这可能导致细胞窘迫和组织损伤增加。我们建议研究METH使用对TBI患者脑灌注、脑代谢和神经功能结局的影响。我们的目的是：1）评估经毒理学试验鉴定为METH检测阳性的受试者在TBI后的脑N-乙酰天冬氨酸（NAA）和乳酸水平（METH TBI）和METH测试阴性的人（非METH TBI），使用质子磁共振（MR）光谱，2）使用定量磁共振灌注成像（pMRI）测量METH TBI与非METH TBI受试者的整体和局部脑灌注，以及3）在METH TBI与非METH TBI受试者中，在损伤后6个月时用神经心理学测试评估认知结果。我们假设1）METH TBI受试者与非METH TBI受试者相比，在挫伤周围组织中将显示较低的NAA和较高的乳酸水平。这些发现将提供质子磁共振波谱学上细胞窘迫增加的证据。2)与非METH TBI受试者相比，METH TBI受试者将具有较低的挫伤周围CBF。3)与非METH TBI受试者相比，METH TBI受试者将具有增加的神经行为缺陷。关于METH在TBI患者中的协同作用知之甚少。这项研究将有助于推进我们对代谢和血流动力学变化的理解，这些变化可能导致继发性脑损伤，并影响在持续TBI之前使用METH的患者的长期神经行为恢复。拟议研究的结果将导致更好地了解METH滥用和TBI的协同效应，并可能为患有这些合并症的患者提供新的治疗方法。此外，这些发现将与公共卫生有关，并可能有助于为未来的公共政策提供信息。这项拟议的研究将提高对急性创伤性脑损伤患者使用甲基苯丙胺的生理和功能后果的理解。这将有助于为这一领域的公共教育和预防工作提供信息。它还可以允许为这一患者群体开发特定的治疗策略。

DESCRIPTION (provided by applicant): Methamphetamine (METH) is a highly addictive drug of abuse that has been increasing in popularity in this country and around the world. Crystal METH is the drug of choice in Hawaii and is considered by far the most significant drug threat. Substance abuse increases risk taking behavior and as a result many victims of traumatic brain injury (TBI) are also using illicit drugs. Traumatic brain injury is also a significant public health problem in the United States and around the world with 1.5 million cases of TBI in this country each year. Both METH and TBI can independently cause direct toxicity to neurons as well as alter cerebral perfusion. This may lead to cellular distress and increased tissue injury. We propose to study the effect of METH use on cerebral perfusion, cerebral metabolism and neurologic outcome in patients with TBI. Our aims are 1) to evaluate the levels of cerebral N-acetyl aspartate (NAA) and lactate after TBI in subjects who test positive for METH as identified by toxicology testing (METH TBI) and in those who test negative for METH (non-METH TBI), using proton magnetic resonance (MR) spectroscopy, 2) to measure global and regional cerebral perfusion using quantitative magnetic resonance perfusion imaging (pMRI) in METH TBI versus non-METH TBI subjects, and 3) to assess cognitive outcome with neuropsychological testing at 6 months after injury in METH TBI versus non-METH TBI subjects. We hypothesize that 1) METH TBI subjects will display lower NAA and higher lactate levels in pericontusional tissue when compared to non-METH TBI subjects. These findings would provide evidence of increased cellular distress on proton MR spectroscopy. 2) METH TBI subjects will have lower pericontusional CBF when compared to non-METH TBI subjects. 3) METH TBI subjects will have increased neurobehavioral deficits when compared to non-METH TBI subjects. Very little is known about the synergistic effects of METH in patients with TBI. This study will help advance our understanding of the metabolic and hemodynamic changes that may lead to secondary brain injury and impact long term neurobehavioral recovery in patients who use METH prior to sustaining a TBI. The results of the proposed study will lead to a better understanding of the synergistic effects of METH abuse and TBI and may lead to new treatments for patients who present with these co-morbidities. In addition, these findings will be pertinent to public health and may help to inform public policy in the future. The proposed study will improve the understanding of the physiologic and functional consequences of methamphetamine use in patients who have suffered an acute traumatic brain injury. This will help inform public education and prevention efforts in this area. It may also allow the development of specific therapeutic strategies for this population of patients.