BIOCHEMICAL MARKERS IN ADULT PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aneurysmal subarachnoid hemorrhage ASAH is a serious event with a 51% case fatality rate. Neurological complications following ASAH are common. Delayed ischemic neurological deficit caused by cerebral arterial vasospasm contributes significantly to morbidity and mortality. Biomarkers may provide early warning of impending neurological decline and stroke from ASAH induced vasospasm. This proposal would initiate a systematic identification and validation of a panel of biochemical markers for acute brain injury resulting from the effects of ASAH, detectable in human cerebrospinal fluid CSF and serum, biological fluids routinely accessible following SAH. Specific Aim 1 assesses the diagnostic and prognostic utility of candidate biomarkers breakdown products to spectrin-SBDPs; tau; UCH-L1; MAP2a/b; myelin basic protein-MBP; S100B by examining relationships between levels of specific biomarkers and injury magnitude e.g. WFNS grading scale, magnitude of hemorrhage e.g. Fisher CT grading, occurrence of secondary ischemia from cerebral vasospasm and outcome e.g. neurological assessments. Sensitivity and specificity of markers, alone and in combination will be determined. Specific Aim 2 assesses the utility of these biomarkers for assessment of oncotic and apoptotic cell death mechanisms by examining relationships between CSF levels of biomarkers and specific pathological events that occur after ASAH. The long-term goal of this research is to produce quantitative ELISA assay systems capable of providing clinically useful diagnostic and prognostic information from both CSF and blood samples.