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.
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.
|Chi, Yueh-Yun; Muller, Keith E (2013) Two-Step Hypothesis Testing When the Number of Variables Exceeds the Sample Size. Commun Stat Simul Comput 42:1113-1125|
|Chi, Yueh-Yun; Gribbin, Matthew; Lamers, Yvonne et al. (2012) Global hypothesis testing for high-dimensional repeated measures?outcomes. Stat Med 31:724-42|