Biochemical Markers in Adult Patients with Aneurysmal Subarachnoid Hemorrhage

描述（由申请人提供）：美国每年约有140万人遭受创伤性脑损伤（TBI）。14，32目前用于评估脑损伤的技术（如MRI和CT）价格昂贵，并且预测结果的能力有限。一个可量化的生物标志物将提供有用的信息，在确定损伤的严重程度和指导实施适当的治疗。在TBI患者中收集CSF样本进行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，并且由于许多患者遭受严重的并发损伤，因此总体人群各不相同。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CSF中生物标志物的同质患者人群，因为这些患者中的许多人将需要脑室外引流作为其护理的标准部分。高达46%的患者发生脑动脉血管痉挛导致的迟发性缺血性神经功能缺损（DIND）22，23，ASAH占美国所有新发卒中的5%。卒中是美国第三大死亡原因，尽管局灶性神经功能缺损有多种原因可能与卒中混淆，但仍经常仅根据临床进行诊断。66生物标志物可提供卒中即将发生衰退的早期预警和脑损伤后可能结局的信息，这两种疾病状态均可在ASAH患者中进行研究。该提案将启动一个系统的识别和验证的一组生化标志物的急性脑损伤和缺血性中风中所见的ASAH患者，检测人脑脊液（CSF）和血清，生物液体常规ASAH后。该项目的具体目标是使用蛋白质组学方法来识别血清样本中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CSF样本中验证它们。将检查生物标志物水平与损伤程度、继发性缺血发生率和结局的关系。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;蛛网膜下腔出血（ASAH）患者同时患有这两种疾病。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，可以开发可用于实时监测患者的技术。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，用于确定最佳护理过程。

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.