Influence of Melatonin on Cerebrovascular Proinflammatory Mediators Expression and Oxidative Stress Following Subarachnoid Hemorrhage in Rabbits

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.

Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage

“…The malondialdehyde (MDA) levels were determined using the method of a previous study. 8 The principle of the assay depends on the reaction of lipid peroxidation products with thiobarbituric acid and formation of products called thiobarbituric acid-reacting substances, which give maximum absorbance at the 535-nm wavelength. The MDA concentrations were given as nanomoles/milligram protein.…”

Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells

“…Several studies with cells, tissues, and whole animals have shown that melatonin inhibits NF-κB either by oxidative stress or PAMPs. Melatonin reduces NF-κB activation in macrophages [42], T cells [43,44], RAW 264.7 cell line [45–47], neuronal tissue and cell culture [47–49], liver [50], kidney [51,52], lung [53], and heart [54]. Studies based on models of inflammatory disease, such as inflammatory bowel disease [55], colitis [56], chronic gastric ulceration model in mice [57], and experimental diabetic neuropathy [58] as well as inflammatory processes, such as hyperalgesia associated with inflammation [59], spinal cord trauma [60], and fulminant hepatic failure [50] in rats describe a reduction of inflammatory output by melatonin.…”

“…Studies based on models of inflammatory disease, such as inflammatory bowel disease [55], colitis [56], chronic gastric ulceration model in mice [57], and experimental diabetic neuropathy [58] as well as inflammatory processes, such as hyperalgesia associated with inflammation [59], spinal cord trauma [60], and fulminant hepatic failure [50] in rats describe a reduction of inflammatory output by melatonin. In addition, when evaluated, the anti-inflammatory effect of melatonin was shown to be mediated by the inhibition of NF-κB nuclear translocation [42,49,54,61–63]. …”

Astaxanthin reduces matrix metalloproteinase-9 expression and activity in the brain after experimental subarachnoid hemorrhage in rats

“…Malondialdehyde (MDA) levels were determined with the method of the previous study (Fang et al, 2009). The principle of the assay depends on the reaction of lipid peroxidation products with thiobarbituric acid and formation of products named as thiobarbituric acid reacting substances, which give maximum absorbance at 535 nm wavelength.…”