Effect of pinealectomy and. melatonin replacement on morphological and biochemical recovery after traumatic brain injury
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.
Available from: Cristina morganti-kossmann
- "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.
Journal of Cerebral Blood Flow & Metabolism 04/2008; 28(4):684-96. DOI:10.1038/sj.jcbfm.9600603 · 5.41 Impact Factor
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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.
Neuro endocrinology letters 10/2007; 28(5):666-70. · 0.80 Impact Factor
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ABSTRACT: So far, several treatment modalities have been attempted to brain protection in cases such as brain trauma, stroke or brain hemorrhage. However, a treatment method that the effect begins immediately and definitely helpful has not been discovered yet. In this study, we aimed to compare the effects of propofol and erythropoietin (Epo) on brain injury caused by oxidative stress and antioxidant properties of these agents after closed head injury (CHI) in rats. For this study, female Wistar Albino rats were divided into five groups: non-traumatic control group, trauma performed group CHI, trauma with propofol (100 mg/kg) intraperitoneally (i.p.), trauma with Epo (5000 U/kg) i.p. and trauma with propofol and Epo performed study groups. Twenty-four hours after CHI, rats were sacrificed and the brains were removed. Superoxide dismutase (SOD), catalase (CAT), xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) levels were measured in brain tissue. MDA and NO levels were decreased significantly in Groups Epo, Propofol and Epo+Propofol than Group CHI (p<0.01). XO activity was significantly lower in Group Epo than Group CHI (p<0.05). Epo and propofol decreased oxidative stress by decreasing MDA and NO level in brain tissue after CHI. However, combination of Epo and propofol has no significant beneficial advantage than Epo or propofol alone.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2008; 32(1):81-6. DOI:10.1016/j.pnpbp.2007.07.016 · 3.69 Impact Factor
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