Evaluation of HS-producing enzymes in cerebrospinal fluid and its relationship with interleukin-6 and neurologic deficits in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE

Recent studies have suggested that HS may be involved in the pathophysiology of subarachnoid hemorrhage (SAH). Endogenous HS is mainly formed by cystathionine β-synthase (CBS), d-amino-acid oxidase (DAO), and 3-mercaptopyruvate sulfotransferase (3-MST) from the substrate cysteine in the central nervous system. In this study, we assessed the expression of CBS, 3-MST, and DAO in cerebrospinal fluid (CSF) from patients with SAH and rats and the expression in the rat brain.

METHODS

CSF samples were collected within 48 h of aneurysm rupture in SAH patients. The CBS, DAO and 3-MST levels in CSF were measured using Western blot analyses, and correlations with the inflammatory parameter Interleukin-6 (IL-6) were assessed. Six months after SAH, the clinical outcomes were assessed.

RESULTS

In human CSF samples, the CBS and DAO protein levels were detected and increased after SAH. However, 3-MST was not detected in the control group CSF but increased after SAH. Strong correlations were observed between the increasing levels of CBS, DAO, and 3-MST and IL-6 2 days after SAH. Furthermore, high CBS, 3-MST and DAO levels in the CSF samples were correlated with poor outcomes at 6 months after SAH onset. We also found that the expression of CBS, DAO and 3-MST in the rat CSF and brain (parietal cortex and hippocampus) increased following SAH. We detected strong correlations between the increases in CBS, 3-MST and IL-6 in the rat CSF and brain samples.

CONCLUSIONS

These results indicate that the upregulated expression of CBS, DAO and 3-MST after SAH was closely associated with the inflammatory response and neurological deficits after SAH.