Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm.

Aneurismal subarachnoid haemorrhage (SAH) is a devastating disease that is associated with significant morbidity and mortality. The mortality is approximately 50%, with 30% of survivors having significant morbidity. There is substantial evidence to suggest that oxidative stress is significant in the development of acute brain injury and cerebral vasospasm following SAH. There are several sources for the excessive generation of free radicals following SAH, including disrupted mitochondrial respiration and extracellular hemoglobin. There is also the upregulation of free radical producing enzymes such as inducible nitric oxide synthase (iNOS), xanthine oxidase, NADPH oxidase (NOX), as well as enzymes involved in the metabolism of arachidonic acid. Additionally, intrinsic antioxidant systems such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are inhibited. Experiments have linked free radicals to the apoptosis of neurons and endothelial cells, BBB breakdown and the altered contractile response of cerebral vessels following SAH. Antioxidant therapy has provided neuroprotection and antispasmotic effects in experimental SAH and some therapies have demonstrated improved outcomes in clinical trials. These studies have laid a foundation for the use of antioxidants in the treatment of aneurismal SAH.