Evaluation of H(2)S-producing enzymes in cerebrospinal fluid and its relationship with interleukin-6 and neurologic deficits in subarachnoid hemorrhage.

Affiliation

Han M(1), Liu D(2), Qiu J(3), Yuan H(3), Hu Q(4), Xue H(5), Li T(3), Ma W(3), Zhang Q(6), Li G(7), Wang Z(8).
Author information:
(1)Department of Physiology, School of Basic Medical Sciences, Shandong University, 44# Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China; Department of Neurosurgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012, P.R. China.
(2)Department of Medical Psychology, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
(3)Department of Physiology, School of Basic Medical Sciences, Shandong University, 44# Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
(4)Department of Neurosurgery, Taian Central Hospital, 29#, Long Tan Road, Taian, Shandong Province, 271000, P.R. China.
(5)Department of Neurosurgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012, P.R. China; Department of Physiology, School of Basic Medical Sciences, Shandong University, 44# Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
(6)Department of Cardiology, The 5th People's Hospital of Jinan, 24297#, Jingshi Road, Jinan, Shandong Province, 250022, P.R. China; Department of Physiology, School of Basic Medical Sciences, Shandong University, 44# Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
(7)Department of Neurosurgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012, P.R. China. Electronic address: [Email]
(8)Department of Physiology, School of Basic Medical Sciences, Shandong University, 44# Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China. Electronic address: [Email]

Abstract

BACKGROUND AND PURPOSE: Recent studies have suggested that H2S may be involved in the pathophysiology of subarachnoid hemorrhage (SAH). Endogenous H2S 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.