Targeted proteomic analysis identifies ACVRL1 as a marker of cerebral edema in aneurysmal subarachnoid hemorrhage

Cerebral edema (CE) is a major component of early brain injury from aneurysmal subarachnoid hemorrhage (SAH). Despite the utility of blood-based protein markers, biomarkers targeting cerebral edema have yet to be developed. We performed a targeted proteomic search analyzing 141 proteins in plasma samples taken from 80 adult patients within 48 hours after aneurysmal rupture to identify plasma biomarkers of cerebral edema. The protein expression profiles were analyzed for associations with a higher level of the subarachnoid hemorrhage early brain edema score measured in admission computed tomography scans. Five differentially expressed proteins—brorin, ectodysplasin A2 receptor, layilin, scavenger receptor class A member 5, and activin A receptor like type 1 (ACVRL1)—were identified. To confirm our findings, in a separate cohort of 75 adult patients with SAH, these biomarker candidates was analyzed using a different confirmatory analytic method—enzyme-linked immunosorbent assay—based on the plasma samples collected within 48 hours after aneurysmal rupture. ACVRL1 levels consistently showed a decrease expression levels as the severity of edema increased. The association between CE and ACVRL1 was significant before and after adjusting for patient factors.