Biochemical Markers in Adult Patients with Aneurysmal Subarachnoid Hemorrhage

描述（由申请人提供）：在美国，每年大约有140万人遭受创伤性脑损伤（TBI）。14,32目前可用的评估脑损伤的技术，如MRI和CT，价格昂贵，预测结果的能力有限。可量化的生物标志物将为确定损伤严重程度提供有用的信息，并指导实施适当的治疗。收集脑脊液样本用于TBI患者的生物标志物检测是一项挑战，因为并非所有患者都需要常规引流，而且由于许多患者存在严重的并发损伤，总体人群各不相同。动脉瘤性蛛网膜下腔出血（ASAH）是一种严重的脑损伤事件。这是一个适合研究脑脊液生物标志物的同质患者群体，因为这些患者中的许多人将需要室外引流作为其护理的标准部分。脑动脉痉挛引起的迟发性缺血性神经功能缺损（DIND）在高达46%的患者中发生22,23，而在美国，ASAH占所有新发卒中的5%。中风是美国第三大死亡原因，尽管有多种病因导致局灶性神经功能障碍，但仍然常常仅凭临床依据进行诊断，这可能与中风相混淆生物标志物可以提供中风即将衰退的早期预警和脑损伤后可能的结果信息，这两种疾病状态都可以在ASAH患者中进行研究。该提案将启动一项系统的识别和验证一组用于急性脑损伤和缺血性卒中的生化标志物，这些标志物可在ASAH患者的脑脊液（CSF）和血清中检测到，ASAH后常规可获得的生物液体。该项目的具体目的是使用蛋白质组学方法在血清样本中识别脑损伤和中风的潜在生物标志物，并使用免疫印迹技术在ASAH患者的脑脊液样本中验证它们。生物标志物水平与损伤程度、继发性缺血的发生和预后的关系将被检查。公共卫生相关性：创伤性脑损伤（TBI）和中风每年分别影响数百万人；动脉瘤性蛛网膜下腔出血（ASAH）患者两者兼有。使用ASAH患者作为这些类型脑损伤的模型来识别血清生物标志物，可能会促进可用于实时监测患者的技术的发展。在床边解释生物标志物水平可以为治疗医生提供更多信息，以确定最佳治疗方案。

DESCRIPTION (provided by applicant): Approximately 1.4 million people sustain a traumatic brain injury (TBI) in the United States every year.14, 32 Currently available technologies for assessing brain injury such as MRI and CT are expensive and have limited ability to predict outcome. A quantifiable biomarker would provide useful information in determining injury severity and guide in the implementation of appropriate treatment. Collecting CSF samples for biomarker testing among TBI patients is a challenge, as not all patients need routine drainage and the overall population is varied because many patients sustain a serious concurrent injury. Aneurysmal subarachnoid hemorrhage (ASAH) is a serious event in which brain injury is inflicted. This is a homogenous patient population suited for studying biomarkers in the CSF, as many of these patients will need extraventricular drainage as a standard part of their care. Delayed ischemic neurological deficit (DIND) from cerebral arterial vasospasm occurs in up to 46% of patients 22, 23 and ASAH accounts for 5% of all new strokes in the US. Stroke is the third leading cause of death in the US and still diagnosis is often made solely on clinical grounds, even though there are multiple causes for focal neurological deficit which may be confused for stroke.66 Biomarkers may provide early warning of impending decline from stroke and information about possible outcome after brain injury, both disease states which can be studied in ASAH patients. This proposal would initiate a systematic identification and validation of a panel of biochemical markers for acute brain injury and ischemic stroke as seen in ASAH patients, detectable in human cerebrospinal fluid (CSF) and serum, biological fluids routinely accessible following ASAH. The specific aim of this project is to use proteomic methods to identify potential biomarkers of brain injury and stroke in serum samples and validate them in CSF samples of ASAH patients using immunoblotting techniques. The relationship of biomarker levels to injury magnitude, occurrence of secondary ischemia and outcome will be examined. PUBLIC HEALTH RELEVANCE: Traumatic brain injury (TBI) and stroke each affect millions of people yearly; aneurysmal subarachnoid hemorrhage (ASAH) patients suffer from both. Using ASAH patients as a model for these types of brain injury to identify serum biomarkers may allow for the development of technology which could be used to monitor patients in real-time. Interpreting biomarker levels at the bedside may then provide treating physicians more information to use in determining the best course of care.