Transforming Growth Factor-β1 in the Cerebrospinal Fluid of Patients with Subarachnoid Hemorrhage: Titers Derived from Exogenous and Endogenous Sources

Abstract

Transforming growth factor-β1 (TGF-β1) is a fibrogenic cytokine that is involved in postinjury repair and is implicated in the etiology of postsubarachnoid hemorrhage (SAH) chronic communicating hydrocephalus. TGF-β1 was measured by enzyme-linked immunosorbant assay (ELISA) in sequential samples of cerebrospinal fluid (CSF) in 11 patients with hydrocephalus after SAH; levels were seen to be biphasically elevated and sources were investigated. TGF-β1 levels were compared with albumin levels that estimated CSF blood content. Control samples from nonhemorrhagic hydrocephalics were tested similarly. Mean total TGF-β1 levels were elevated to 4400 ± 3435 (±SD) pg/mL greater than control levels of 97 ± 42 at 1 to 2 days posthemorrhage. Thereafter, levels fell to 714 ± 401 by 5 to 6 days posthemorrhage, then rose to a second peak of 1667 ± 774 at 9 to 10 days posthemorrhage, remaining significantly increased until 19 days posthemorrhage ( P = 0.007). The first peak probably derived from extravasated platelets and correlated with increased albumin levels in the CSF. The second TGF-β1 peak rose greater than CSF albumin levels that had stabilized at this time, and thus was attributed to a tissue-specific response rather than a re-bleed. TGF-β1 was detected in the choroid secretory epithelium from controls, but levels were greater in SAH patients at 10 to 12 days posthemorrhage. The authors conclude that the elevated levels of TGF-β1 in CSF after SAH are derived initially from blood and later from endogenous sources such as the choroid plexus.