Cerebrospinal fluid calcium, apoE protein and genotype in individuals with and without cerebral vasospasm after subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a hemorrhagic stroke subtype affecting 30,000 Americans per year. The most common cause of secondary injury after SAH is cerebral vasospasm (CV). Currently, there are no biomarkers to identify risk for CV. Apolipoprotein E (apoE) is a protein with potential to alter tone of cerebral vessels by influencing intracellular calcium homeostasis. ApoE has isoform specific effects on intracellular calcium (Ca++) level, cerebral vessel tone, and potentially CV. The overall objective of this project was to describe the relationship between apoE genotype (APOE), apoE protein level, calcium level and presence of CV after SAH. This study included individuals age 18--75 with a diagnosis of severe SAH from an aneurysmal source. Daily cerebrospinal fluid samples were drawn from a drainage catheter. APOE genotyping was performed using standard restriction fragment length polymorphism techniques. The sample was dichotomized based on APOE epsilon4 allele presence. Daily apoE protein levels were analyzed using an enzyme linked immunoassay. Ca++ level was analyzed using potentiometry. CV was verified using cerebral angiogram, computed tomographic angiogram, or elevated transcranial dopplers the entire group were lower than normal and associated with one another. Overall and daily apoE protein levels were higher in individuals with an APOE epsilon4 allele but there was no association with CV. Overall Ca++ level was higher in the individuals without CV, however daily mean was not significantly different between the two CV groups. Overall and daily mean Ca++ levels were higher in individuals with an APOE epsilon4 allele. This project further describes the relationship between apoE, Ca++ and neurologic disease, however more work is required before either CSF apoE or Ca++ can be used as a predictor of CV.