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Chronic Subdural Hematoma (CSH) may be challenging to manage due to neurological complications and frequent recurrence. The pathophysiology of fluid collection in CSHs is incompletely understood and the role of water and cation cotransporters in the movement of fluid from dural capillary/venous complexes into the dural border zone and hematomas is unknown.  In the present study, normal dura was collected at autopsy from 9 fetal, 6 neonatal or infant, 11 adult and 16 aged patients. CSHs were collected from 15 surgical specimens. Na-K-2Cl cotransporter (NKCC1) and aquaporin 1 (AQP1) were evaluated using immunohistochemistry.  In the normal dura, NKCC1 immunoreactivity was extensive in neonatal, infant and adult capillaries. NKCC1 was not detected in arterioles and large venules in the fetal and adult dura or in unlined channels at any age. AQP1 was extensive in capillaries in all fetal, infant, aged and 82% of adult dural samples. In venules, AQP1 was extensive in most immature and adults. In CSHs, NKCC1 and AQP1 were extensive in capillaries and sinusoids in the outer dural membrane of each case and exhibited an overlapping distribution.  This study shows that NKCC1 and AQP1 are present on endothelial cells in the developing and adult dura and likely participate in fluid and ion movement from dural and hematoma capillaries into CSHs. Potential pharmacological interventions using NKCC1 inhibitors such as bumetanide and AQP1 inhibitors, along with other agents inhibiting angiogenic factors, should augment current management options and reduce the morbidity and mortality of CSHs.

Identification of NKCC1 and Aquaporin 1 in Blood Vessels of Human Dura and Chronic Subdural Hematomas. A New Target for Bumetanide?