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

Abstract

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.

Genetic Elimination of eNOS Reduces Secondary Complications of Experimental Subarachnoid Hemorrhage

“…26,27 Increased iNOS activity could produce more ROS and aggravate brain injury and large artery vasospasm. [28][29][30] Yatsushige et al, 31 however, found that inhibiting the increase in iNOS after SAH in rats did not reduce blood-brain barrier breakdown, brain edema, neuron death, or mortality. Neuronal NOS has been less studied after SAH.…”

Aneurysmal Subarachnoid Hemorrhage Causes Injury of the Ascending Reticular Activating System: Relation to Consciousness

“…25 Although the pathogenetic mechanisms of neurologic injury following SAH have not been clearly elucidated, there are several possible mechanisms: vasospasm, cortical ischemia, microthromboemboli, hydrocephalus, free radical injury, and inflammation. 4,[28][29][30] However, no study on the pathogenetic mechanism of injury of the lower portion of the ARAS between the reticular formation and the intralaminar thalamic nuclei following SAH has been reported.…”

3,4-Dihydroxyphenylethanol alleviates early brain injury by modulating oxidative stress and Akt and nuclear factor-κB pathways in a rat model of subarachnoid hemorrhage

“…EBI is the main cause of high mortality and morbidity of patients with SAH, and oxidative stress has been demonstrated to play a key role in the development of EBI (5,28,29). The balance of the oxidation and antioxidant systems in the body is broken following SAH; oxidative damage exceeds the capacity of the body's antioxidant defense system, and a large number of oxygen free radicals induce lipid peroxidation, protein denaturation and DNA damage, causing damage to the BBB and pathological changes such as cell death in the brain (28). In the present study, DOPET markedly attenuated the MDA contents and enhanced the activities of SOD, CAT and GSH-PX in the brains of SAH model rats.…”