Abstract
The aim of this study is to analyze whether melatonin administration influenced the nuclear factor-kappa B (NF-κB) activity, proinflammatory cytokines expression, and oxidative response in the basilar artery after SAH. A total of 48 rabbits were randomly divided into four groups: control group, SAH group, SAH + vehicle group, and SAH + melatonin group. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. The melatonin was administered intraperitoneally at a dose of 5 mg/kg/12 h simultaneously with SAH from day 0 to day 5. The basilar arteries were extracted on day 5 after SAH. As a result, we found that vascular inflammation and oxidative stress were induced in all SAH animals. In animals given melatonin, basilar arterial NF-κB and pro-inflammatory cytokines were decreased in comparison to vehicle-treated animals. Measures of oxidative stress also showed significant downregulation after melatonin treatment. Furthermore, administration of melatonin prevented vasospasm on day 5 following SAH. In conclusion, post-SAH melatonin administration may attenuate inflammatory response and oxidative stress in the spasmodic artery, and this may be one mechanism involved in the therapeutic effect of melatonin on the subsequent vasospasm after SAH.
Highlights
Cerebral vasospasm is the most common cause of disability and death in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) [1]
The main findings of this study are that (1) vascular inflammatory mediators were induced after SAH and could be remarkably repressed when treated with melatonin; (2) the increased lipid peroxidation in the artery tissues could be significantly downregulated after melatonin injections following experimental SAH; (3) after melatonin administration, the postSAH reduced antioxidative status was ameliorated in this two-hemorrhage model; (4) in agreement with the previous research [5], treatment with melatonin prevented cerebral vasospasm of the basilar arteries in rabbits
These findings suggest for the first time that melatonin could regulate vascular inflammation and oxidative stress, and this may be one mechanism by which melatonin attenuates the development of cerebral vasospasm after SAH
Summary
Cerebral vasospasm is the most common cause of disability and death in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) [1]. Cerebral vasospasm is commonly caused by the presence of blood products, especially oxyhemoglobin (OxyHb) in the subarachnoid space. Even though the trigger role of OxyHb in the developing vasospasm is well known, the exact mechanism(s) of vasospasm is still unknown. The possible mechanisms may include: upregulated vascular inflammation, endothelial apoptosis, increased free radical products and oxidative stress, adenosine diphosphate- (ADP-) induced vasomotor changes, inhibition of nitric oxide (NO) pathway, protein kinase C (PKC) pathway in vascular smooth muscle, among which inflammation and oxidative stress both play important roles in the pathological process of vasospasm [2,3,4]. Several studies on experimental models of SAH have demonstrated that melatonin can prevent vasospasm [5,6,7]; the exact mechanism of vasoprotective effect is still unknown.
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