Malondialdehyde, glutathione peroxidase, and superoxide dismutase in cerebrospinal fluid during cerebral vasospasm in monkeys.

Cerebral vasospasm may result from lipid peroxidation induced by oxyhemoglobin in the subarachnoid space after subarachnoid hemorrhage. To test this theory, vasospasm was induced in monkeys by intrathecal injections of oxyhemoglobin or supernatant fluid from autologous blood incubated in vitro. Concentration of malondialdehyde (MDA), a product of lipid peroxidation, was elevated in cerebrospinal fluid (CSF) in association with vasospasm caused by oxyhemoglobin and supernatant fluid. Intrathecal injections of methemoglobin or bilirubin did not cause vasospasm or increased CSF MDA. Activity of glutathione peroxidase in CSF increased significantly after injection of oxyhemoglobin and methemoglobin. There were no significant changes in CSF superoxide dismutase activity although there was a trend towards higher activities in animals treated with oxyhemoglobin, methemoglobin, bilirubin, and supernatant fluid. These results show oxyhemoglobin-induced vasospasm is associated with MDA and lipid peroxidation in the subarachnoid space. Furthermore, detection of peroxidation products after injection of oxyhemoglobin in the absence of erythrocyte membranes indicates that oxyhemoglobin may directly damage cerebral arteries and brain by inducing lipid peroxidation in these structures. Depletion of free-radical scavenging enzymes in CSF did not seem necessary for development of vasospasm. In fact, there was a tendency for vasospasm to elevate enzyme activities, as if production of scavengers was induced by excess free radicals in the subarachnoid space.