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: 2.58). 11/2006; 24(6):357-63. DOI: 10.1016/j.ijdevneu.2006.08.003
Source: PubMed


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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    • "Acute brain damage may cause an increase in the amount of ROT due to acceleration of certain excitotoxic amino acid levels such as glutamate. This event leads to the development of parenchymal damage[3,4,19,22,26]. Endogenous and exogenous defense mechanisms are the most important sources in inhibiting oxidative stress[3]. If endogenous non-enzymatic antioxidants, such as glutathione , ascorbic acid, and alpha tocopherol, are incapable of inactivating the free radicals that form during trauma, they[26]. "
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    ABSTRACT: Background: The purpose of our study was to investigate the effect of ginseng on antioxidant enzyme levels in brain damage following experimental diffuse head trauma in rats. The neuroprotective effect of ginseng was also studied. Methods: In this study, rats were divided into four groups, and the rats in group 1 received no intervention. In group 2, the rats were administered 50 mg/kg ginseng, injected intraperitoneally at 1, 24 and 48 h, and the effect of ginseng on normal tissues was studied. No drugs were administered to the rats in group 3 who had previously experienced diffuse head trauma using Feeney's falling weight method. In group 4, rats underwent Feeney's falling weight method, leading to diffuse head trauma, and they were given 50 mg/kg ginseng intraperitoneally 1, 24 and 48 h after head trauma. Rats were killed 72 h after head trauma and their brain tissues extracted for histopathological and biochemical studies. Results: Histopathological study of brain cross sections in the trauma group demonstrated neurons in the trauma region and surrounding area, which generally had a dark-colored eosinophilic cytoplasm and a pyknotic nucleus, while the nuclei of neurons were located peripherally. However, brain cross sections in group 4 from rats given ginseng after head trauma showed fewer neurons with eosinophilic cytoplasm, pyknotic and peripheral nuclei in the trauma region and surrounding area. No statistically significant difference in the tissue SOD level was observed; however, the GSH Px level in group 4 was significantly reduced compared to that in group 3. Conclusions: After affecting the GSH Px level and reducing histopathological scores, ginseng was found to display antioxidant and neuroprotective activity.
    Full-text · Article · Mar 2013 · Acta Neurochirurgica
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    • "Therefore, further preclinical and clinical studies are needed to clarify Endogenous CSF melatonin increases after TBI MA Seifman et al the precise nature of any potential relationships between melatonin and oxidative stress and/or inflammation. Provided these beneficial roles of melatonin were further validated in animal models of TBI and in concert with existing data that show such an effect (Ates et al, 2006), a future direction in the study of melatonin post-TBI could include clinical administration of melatonin to these patients. "
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    ABSTRACT: Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F2alpha (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28+/-0.92 versus 1.47+/-0.35 pg/mL, P<0.0005). Isoprostane levels also increased in both CSF (127.62+/-16.85 versus 18.28+/-4.88 pg/mL, P<0.0005) and serum (562.46+/-50.78 versus 126.15+/-40.08 pg/mL (P<0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury (r=0.563, P=0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate (r=0.369, P=0.049) and glutamate (r=0.373, P=0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.
    Full-text · Article · Apr 2008 · Journal of Cerebral Blood Flow & Metabolism
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    ABSTRACT: Melatonin is a potent antioxidant agent and an anti-aging hormone. Serum melatonin level declines during the menopause. Estradiol, a neuroprotective ovarian hormone, also decreases during the menopause. The purpose of this study is to evaluate the effect of melatonin supplementary on peripheral nerve function in the ovariectomized (OVX)-aged rats. Randomly selected OVX-aged Wistar rats received injections of melatonin (5 or 20 mg/kg) daily either two or six weeks. Nerve conduction velocities and distal latencies were determined from the propagation of action potential recorded by using an extracellular electrophysiological technique. The mean distal latencies of melatonin-treated groups were shorter than that of the control group. Thus, the nerve conduction velocity was significantly greater in both two weeks and six weeks melatonin treated groups as compared to the controls (p<0.001). Melatonin alleviates the electrophysiological properties of the sciatic nerve in OVX-aged rats. Thus, melatonin supplementary may have a potential clinical application for the treatment of postmenopausal peripheral nerve degeneration.
    No preview · Article · Oct 2007 · Neuro endocrinology letters
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