Increased Plasma Levels of Thrombin-Cleaved Osteopontin in Patients with Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage

Osteopontin (OPN), a matricellular protein, is produced as a full-length OPN (FL-OPN) and cleaved by thrombin, thus generating the N-terminal half of OPN (OPN N-half) with new functions. Although plasma FL-OPN levels have been associated with neurovascular events after aneurysmal subarachnoid hemorrhage (SAH), plasma OPN N-half levels have never been investigated. In this study, prospective clinical data and plasma samples were collected from 108 consecutive SAH patients with ruptured aneurysms undergoing acute treatment via surgery, and FL-OPN and OPN N-half levels were measured in plasma with a particular focus on delayed cerebral infarction (DCIn), which has the greatest impact on outcomes. Plasma FL-OPN and OPN N-half levels were intercorrelated and significantly higher in patients with DCIn at days 10–12 post-SAH; a greater area under the receiver-operating characteristic curve was observed for OPN N-half levels, with a cut-off value of 70.42 pmol/L. Multivariate analyses revealed that plasma OPN N-half levels of ≥70.42 pmol/L at days 10–12 were independently associated with DCIn development (adjusted odds ratio, 5.65; 95% confidence interval, 1.68–18.97; p = 0.005). Based on the findings of this study and previous reports, an increase in the OPN N-half level may be indicative of a protective mechanism against DCIn development, and, thus, it holds promise as a new therapeutic target against DCIn after aneurysmal SAH.