THE EFFECT OF APOE ON OUTCOMES IN TBI ADULTS

APOE 对成人 TBI 结局的影响

• 批准号: 6539371
• 负责人: Mary E. Kerr
• 金额: $ 48.61万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539371
• 关键词: adult human (21+); alleles; apolipoprotein E; aspartate; brain circulation; brain injury; brain metabolism; cerebrospinal fluid; clinical research; functional ability; genetic susceptibility; genotype; glutamates; human subject; intracranial pressure; longitudinal human study; neural transmission; neuropsychological tests; oxygen consumption; trauma

DESCRIPTION (As Adapted from the Investigator's Abstract): Mortality and morbidity of patients following a traumatic brain injury (TBI) remain extremely high. TBI induces neuronal injury as evidenced by a misalignment and compaction of the neurofilaments and dispersion of the microtubules within the axon that effect neurotransmission. Apolipoprotein E (ApoE) is responsible for the transportation of lipids within the brain, assists in neurotransmission and maintains the structural integrity of the microtubule within the neuron. The genotype for ApoE (APOE) has been linked to microtubule regeneration and permeability within the neuron contributing to brain edema, which plays a major role in outcomes after TBI. We hypothesize that individuals with the APOE4 allele will have greater difficulty in rebuilding microtubules as compared to those without APOE4 alleles and this difference will be observed by clinical manifestations of decreased flow, metabolism and altered neurotransmission. Thus, the purpose of this study is to examine APOE genotype and its relationship to the cerebrovascular, metabolic and neurotransmitter responses and functional outcomes following a TBI. The research questions are: 1) Is there a difference in the intracranial pressure (ICP), cerebral perfusion pressure, cerebral blood flow, arterial-jugular venous oxygen difference, arterial-jugular venous glucose difference, cerebral oxygen metabolism and lactate/pyruvate ratio during the first 5 days following TBI between patients with and without APOE4 alleles while controlling for intensity of ICP therapy? 2) Is there a difference in aspartate and glutamate levels in the cerebrospinal fluid during the first 5 days following TBI between those patients with and without APOE4 alleles? 3) Is there a difference in the functional outcomes (mortality, and neuropsychologic evaluation measured using the Glasgow Outcome Scale, Disability Rating Scale and the Neurobehavioral rating scale) at 3 and 6 months after TBI between patients with and without APOE4 alleles? If the hypotheses are supported and there are genetic differences in the brain's tissue metabolism and blood flow response following TBI that impact on outcomes, the results could lead to a new vista of nursing, medical and pharmacologic therapies.

描述（改编自研究者摘要）：死亡率和 创伤性脑损伤（TBI）后患者的发病率仍然非常高， 高TBI诱导神经元损伤，如通过未对准和压实所证明的 轴突内的神经丝和微管的分散， 影响神经传递。载脂蛋白E（ApoE）负责 脂质在脑内的运输，协助神经传递， 维持神经元内微管的结构完整性。的 ApoE基因型（APOE）与微管再生有关， 神经元内的渗透性导致脑水肿，这是一个主要的 在TBI后的结果中的作用。我们假设携带APOE 4基因的个体 与等位基因相比，等位基因重建微管的难度更大 没有APOE 4等位基因的人，这种差异将通过临床观察 表现为血流减少、代谢和神经传递改变。 因此，本研究的目的是检测APOE基因型及其与 与脑血管、代谢和神经递质反应的关系 和功能结果。研究问题是：1） 颅内压（ICP）、脑血流灌注 血压，脑血流量，动脉-颈静脉氧差， 动脉-颈静脉葡萄糖差、脑氧代谢和 患者之间TBI后前5天内的乳酸/丙酮酸比值 有和没有APOE 4等位基因，同时控制ICP治疗的强度？ 2)脑脊髓中的天冬氨酸和谷氨酸水平是否存在差异 在TBI后的前5天内， 没有APOE 4等位基因的人吗3)功能结果是否存在差异 （死亡率和使用格拉斯哥结局测量的神经心理学评估 量表、残疾评定量表和神经行为评定量表） 有无APOE 4等位基因的患者TBI后3个月的差异？如果 假设得到支持，大脑的遗传差异 TBI后的组织代谢和血流反应， 结果，结果可能会导致护理，医疗和 药物治疗