Claudin proteins and hemorrhage severity in aneurysmal subarachnoid hemorrhage: Correlation with modified Fisher score but not functional outcome.

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.