Glutathione peroxidase and subarachnoid hemorrhage: implications for the role of oxidative stress in cerebral vasospasm.

Objective: Worldwide, cerebral vasospasm after subarachnoid hemorrhage (SAH) has an estimated morbidity and mortality of 1.2 million annually. While it has long been suspected that reactive oxygen species play a major role in the etiology of cerebral vasospasm after SAH, promising results in animal work were not borne out in human clinical trials, despite intensive research effort. The purpose of this study is to investigate the role of glutathione peroxidase in the SAH cerebrospinal fluid milieu. Methods: We utilized commercially available kits for the quantitation of glutathione peroxidase 1 (glutathione peroxidase) activity and oxygen radical capacity and sodium dodecyl sulfate polyacrylamide gel electrophoresis with Western blotting with specific antibodies to human glutathione peroxidase to determine the enzyme content of the cerebrospinal fluid samples. Human cerebrospinal fluid was obtained in an Institutional Review Board-exempt manner for this study in the following groups: control (no SAH), CSF_C (SAH but no vasospasm on angiography) and CSF_V (SAH with clinical and angiographic vasospasm). Results: We found that glutathione peroxidase activity is significantly higher in CSF_V compared with CSF_C, and this is reflected in a higher total oxidative capacity in CSF_V. Despite similar levels of glutathione peroxidase protein, CSF_V had significantly greater activity than CSF_C. Discussion: These results further elucidate previous research from this laboratory, showing increased oxidative stress in CSF_V compared with CSF_C. In conclusion, there appears to be increased glutathione peroxidase activity in CSF_V, despite there being increased levels of oxidative stress markers, suggesting overwhelming oxidative stress may play a role in cerebral vasospasm after SAH. [ABSTRACT FROM AUTHOR]