Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a critical condition characterized
by blood-brain barrier (BBB) disruption. Tight junction proteins, claudin-3 (CLDN3)
and claudin-5 (CLDN5), are key regulators of BBB integrity and may serve as biomarkers
of hemorrhage severity. Methods: In this prospective cohort study, 200 patients with
aSAH were evaluated. Serum CLDN3 and CLDN5 levels were measured on days 1, 5, and
9 post-ictus and compared with healthy and aneurysm-bearing controls. Patients were
stratified by modified Fisher Score (mFS), World Federation of Neurosurgical Societies
(WFNS) score, and 3-month modified Rankin Scale (mRS). Associations with complications,
including delayed cerebral ischemia (DCI) and infection, were also assessed. Results:
CLDN3 and CLDN5 levels were significantly elevated in aSAH patients compared to controls
( p <0.01 and p <0.0001, respectively), with CLDN5 levels consistently higher than
CLDN3 at all time points ( p <0.0001). CLDN5 levels were consistently higher than
CLDN3 at all measured time points, and neither CLDN3 nor CLDN5 showed significant
temporal variation between days 1, 5, and 9. Both markers showed significant positive
correlation with mFS, with higher levels observed in mFS3 and mFS4 groups ( p <0.05
to p <0.0001). No association was found between CLDN3 and 5 levels and WFNS score,
3-month mRS, age, sex, comorbidities, inflammatory markers, or DCI. Conclusion: Elevated
serum CLDN3 and especially CLDN5 levels reflect hemorrhage extent and potential BBB
disruption in aSAH. Their strong correlation with mFS suggests utility in grading
imageological hemorrhagic severity, though not in predicting long-term functional
outcomes. CLDN5 emerges as a promising biomarker for early assessment of BBB integrity
in neurovascular injury.
