Effect of pinealectomy and. melatonin replacement on morphological and biochemical recovery after traumatic brain injury

Department of Biochemistry, Inonu University, Malatia, Malatya, Turkey
International Journal of Developmental Neuroscience (Impact Factor: 2.92). 11/2006; 24(6):357-63. DOI: 10.1016/j.ijdevneu.2006.08.003
Source: PubMed

ABSTRACT Numerous studies showed that melatonin, a free radical scavenger, is neuroprotective. In this study, we investigated the effect of pinealectomy and administration of exogenous melatonin on oxidative stress and morphological changes after experimental brain injury. The animals were divided into six groups, each having 12 rats. Group 1 underwent craniotomy alone. Group 2 underwent craniotomy followed by brain trauma and received no medication. Group 3 underwent craniotomy followed by brain trauma and received melatonin. Group 4 underwent pinealectomy and craniotomy alone. Group 5 underwent pinealectomy and craniotomy followed by brain injury and received no medication. Group 6 underwent pinealectomy and craniotomy followed by brain trauma and received melatonin. Melatonin (100 mg/kg) was given intraperitoneally immediately after trauma to the rats in Groups 3 and 6. Pinealectomy caused a significant increase in the malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), and xanthine oxidase (XO) levels, and a decrease in GSH levels as compared to the control group. Trauma to pinealectomized rats causes significantly higher oxidative stress. Exogeneous melatonin administration significantly reduced MDA, XO and NO levels, increased GSH levels, and attenuated tissue lesion area. These findings suggest that reduction in endogenous melatonin after pinealectomy makes the rats more vulnerable to trauma, and exogenous melatonin administration has an important neuroprotective effect.

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    ABSTRACT: Traumatic brain injury (TBI) is frequently associated with abnormal blood-brain barrier function, resulting in the release of factors that can be used as molecular biomarkers of TBI, among them GFAP, UCH-L1, S100B, and NSE. Although many experimental studies have been conducted, clinical consolidation of these biomarkers is still needed to increase the predictive power and reduce the poor outcome of TBI. Interestingly, several of these TBI biomarkers are oxidatively modified to carbonyl groups, indicating that markers of oxidative stress could be of predictive value for the selection of therapeutic strategies. Some drugs such as corticosteroids and progesterone have already been investigated in TBI neuroprotection but failed to demonstrate clinical applicability in advanced phases of the studies. Dietary antioxidants, such as curcumin, resveratrol, and sulforaphane, have been shown to attenuate TBI-induced damage in preclinical studies. These dietary antioxidants can increase antioxidant defenses via transcriptional activation of NRF2 and are also known as carbonyl scavengers, two potential mechanisms for neuroprotection. This paper reviews the relevance of redox biology in TBI, highlighting perspectives for future studies.
    01/2014; 2014:723060. DOI:10.1155/2014/723060
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    ABSTRACT: Melatonin is an endogenous hormone mainly produced by the pineal gland whose dysfunction leads to abnormal sleeping patterns. Changes in melatonin have been reported in acute traumatic brain injury (TBI); however, the impact of environmental conditions typical of the intensive care unit (ICU) has not been assessed. The aim of this study was to compare daily melatonin production in three patient populations treated at the ICU to differentiate the role of TBI versus ICU conditions. Forty-five patients were recruited and divided into severe TBI, trauma without TBI, medical conditions without trauma, and compared to healthy volunteers. Serum melatonin levels were measured at four daily intervals at 0400 h, 1000 h, 1600 h, and 2200 h for 7 days post-ICU admission by commercial enzyme linked immunosorbent assay. The geometric mean concentrations (95% confidence intervals) of melatonin in these groups showed no difference being 8.3 (6.3-11.0), 9.3 (7.0-12.3), and 8.9 (6.6-11.9) pg/mL, respectively, in TBI, trauma, and intensive care cohorts. All of these patient groups demonstrated decreased melatonin concentrations when compared to control patients. This study suggests that TBI as well as ICU conditions, may have a role in the dysfunction of melatonin. Monitoring and possibly substituting melatonin acutely in these settings may assist in ameliorating long-term sleep dysfunction in all of these groups, and possibly contribute to reducing secondary brain injury in severe TBI.
    Frontiers in Neurology 11/2014; 5:237. DOI:10.3389/fneur.2014.00237
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    ABSTRACT: Introduction Melatonin is a hormone which is known to be a powerful cardioprotective agent due to its free radical-scavenging properties. This study was carried out to evaluate whether melatonin administration prior to irradiation would have a protective effect on cardiac histopathological changes in an experimental rat model. Methods Rats were divided into four groups. Single dose of 18 Gy radiation and sham radiation exposure were used in related groups. 50 mg/kg dose of melatonin were injected intraperitonally 15 minutes prior to radiation exposure. Analyses and assessments were performed 6 months after radiation exposure. Results Severe myocardial fibrosis was observed prominently in three regions; the apex, tips of papillary muscles and adjacent to the atrioventricular valves. Inflammation was found to be more in irradiated groups. Increased inflammation and fibrosis were in concordance. The number of mast cells was found to be decreased in irradiated groups. Myocyte necrosis and fibrosis were diminished with melatonin while vasculitis was prevented. Conclusions Elementary pathological lesions of radiation-induced heart disease (RIHD) are fibrosis, vascular damage, vasculitis and myocyte necrosis. Development of vasculitis was prevented by the use of melatonin. Fibrosis and necrosis were prominently decreased. Prevention of RIHD with the use of melatonin at the long term is encouraging according to the histopathological results.
    Pathology - Research and Practice 09/2014; 210(12). DOI:10.1016/j.prp.2014.08.006 · 1.56 Impact Factor