PAR-1 Expression in Chronic Subdural Hematoma: Potential Association with Vascular Permeability

Chronic subdural hematoma (CSDH) is a common neurosurgical disease in the elderly, characterized by inflammation, neovascularization, and increased vascular permeability. Although protease-activated receptor-1 (PAR-1) is known to regulate vascular permeability and is implicated in chronic inflammatory diseases, its role in CSDH remains unclear. In this exploratory study, we investigated PAR-1 expression in the dura mater and outer membrane of patients with CSDH compared with controls. Age- and sex-matched cases (six CSDH, five controls) were selected for analysis. Immunohistochemistry for PAR-1 and zonula occludens-1 (ZO-1), along with mRNA expression analysis, were performed. Histologically, the outer membrane of CSDH exhibited cellular clustering and strong PAR-1 immunoreactivity in vascular structures, whereas the dura mater from both groups showed no significant PAR-1 staining. ZO-1 expression was preserved in the vasculature of the outer membrane in CSDH and the dura mater of both groups. mRNA analysis revealed a trend toward higher PAR-1 and lower ZO-1 expression in CSDH, though not statistically significant. The group effect (p = 0.24, analysis of covariance [ANCOVA] t-test) represents the adjusted difference in ZO-1 expression between CSDH and control groups after accounting for PAR-1 levels. The main effect of PAR-1 (p = 0.15, ANCOVA t-test) reflects the overall association between PAR-1 and ZO-1 expression across samples. This study provides the first evidence of PAR-1 expression in the outer membrane of CSDH, suggesting a role in promoting local vascular hyperpermeability. These findings highlight PAR-1 as a possible biomarker and therapeutic target in CSDH. Further studies with larger cohorts and quantitative analyses are warranted to clarify the molecular mechanisms underlying vascular dysfunction in CSDH.