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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melatonin (0.3 to 0.4 mg/kg) dissolved in 0.5 ml dimethylsulphoxide (DMSO) was injected i.v. into six baboons, and their cardiovascular parameters were monitored. Left ventricular end-diastolic and end-systolic volumes, stroke volume, cardiac output, and left ventricular ejection fraction were measured, using conventional radionuclide ventriculography, and compared to normal values previously established. These parameters were also measured after an i.v. administration of only DMSO. The only statistical significant change due to melatonin was the increase in the cardiac output and left ventricular ejection fraction. With the reduced heart rate the increase in cardiac output implies a positive inotropic action on the heart by melatonin. There are indications that DMSO possibly suppresses cardiovascular actions of melatonin.
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PMID:The effect of intravenous administration of melatonin on cardiovascular parameters of the baboon (Papio ursinus). 179 27

In this study, we injected 10 mg/kg kainate i.p. into rats. This resulted in a brain injury, which we quantified in the hippocampus, the amygdala, and the pyriform cortex. Neuronal damage was preceded by a set of typical behavioral signs and by biochemical changes (noradrenaline decrease and 5-hydroxyindoleacetic acid increase) in the affected brain areas. Melatonin (2.5 mg/kg) was injected i.p. four times: 20 min before kainate, immediately after, and 1 and 2 h after the kainate. The cumulative dose of 10 mg/kg melatonin prevented kainate-induced neuronal death as well as behavioral and biochemical disturbances. A possible mechanism of melatonin-provided neuroprotection lies in its antioxidant action. Our results suggest that melatonin holds potential for the treatment of pathologies such as epilepsy-associated brain damage, stroke, and brain trauma.
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PMID:Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. 866 66

This review summarizes the present knowledge on melatonin in several areas on physiology and discusses various prospects of its clinical utilization. Ever increasing evidence indicates that melatonin has an immuno-hematopoietic role. In animal studies, melatonin provided protection against gram-negative septic shock, prevented stress-induced immunodepression, and restored immune function after a hemorrhagic shock. In human studies, melatonin amplified the antitumoral activity of interleukin-2. Melatonin has been proven as a powerful cytostatic drug in vitro as well as in vivo. In the human clinical field, melatonin appears to be a promising agent either as a diagnostic or prognostic marker of neoplastic diseases or as a compound used either alone or in combination with the standard cancer treatment. Utilization of melatonin for treatment of rhythm disorders, such as those manifested in jet lag, shift work or blindness, is one of the oldest and the most successful clinical application of this chemical. Low doses of melatonin applied in controlled-release preparation were very effective in improving the sleep latency, increasing the sleep efficiency and rising sleep quality scores in elderly, melatonin-deficient insomniacs. In the cardiovascular system, melatonin seems to regulate the tone of cerebral arteries; melatonin receptors in vascular beds appear to participate in the regulation of body temperature. Heat loss may be the principal mechanism in the initiation of sleepiness caused by melatonin. The role of melatonin in the development of migraine headaches is at present uncertain but more research could result in new ways of treatment. Melatonin is the major messenger of light-dependent periodicity, implicated in the seasonal reproduction of animals and pubertal development in humans. Multiple receptor sites detected in brain and gonadal tissues of birds and mammals of both sexes indicate that melatonin exerts a direct effect on the vertebrate reproductive organs. In a clinical study, melatonin has been used successfully as an effective female contraceptive with little side effects. Melatonin is one of the most powerful scavengers of free radicals. Because it easily penetrates the blood-brain barrier, this antioxidant may, in the future, be used for the treatment of Alzheimer's and Parkinson's diseases, stroke, nitric oxide, neurotoxicity and hyperbaric oxygen exposure. In the digestive tract, melatonin reduced the incidence and severity of gastric ulcers and prevented severe symptoms of colitis, such as mucosal lesions and diarrhea.
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PMID:Prospects of the clinical utilization of melatonin. 973 May 80

Free radicals have been implicated in neuronal injury during ischemia reperfusion in stroke. Therefore, in the present study, melatonin, a potent antioxidant, was studied in male Wistar rats subjected to 2 h of transient middle cerebral artery occlusion. Melatonin (10, 20 and 40 mg/kg i.p.) was administered four times in an animal at the time of middle cerebral artery occlusion, 1 h after middle cerebral artery occlusion, at the time of reperfusion and 1 h after reperfusion. Two hours after reperfusion, rats were euthanized for estimation of oxidative stress markers (malondialdehyde and reduced glutathione). The doses of 20 and 40 mg/kg of melatonin significantly attenuated the raised level of malondialdehyde (287+/-28, 279+/-52 nmol/g wet tissue, respectively) as compared to the levels (420+/-61 nmol/g wet tissue) in vehicle-treated middle cerebral artery-occluded rats. There was an insignificant change in levels of reduced glutathione at these doses (95+/-42, 88.7+/-36 microg/g wet tissue, respectively) as compared to those in the vehicle-treated middle cerebral artery-occluded rats (108.21+/-21 microg/g wet tissue). However, there was an insignificant difference between 20 and 40 mg/kg treated rats. Therefore, the dose of 20 mg/kg i.p. was used to evaluate the neuroprotective effect by using diffusion-weighted imaging (30 min after reperfusion), assessing the neurological deficit (24 h after middle cerebral artery occlusion) and estimating oxidative stress markers (72 h after middle cerebral artery occlusion). In the 20 mg/kg melatonin-treated group, percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated (9.8+/-3.9) as compared to that in the vehicle-treated group (21.4+/-4.7). The neurological deficit was significantly improved in the melatonin group (1.8+/-0.06) as compared to that in the vehicle-treated (2.9+/-0.38) group. The level of malondialdehyde (321.4+/-31 nmol/g wet tissue) and reduced glutathione (142.6+/-13 microg/g wet tissue) in the melatonin-treated group was also significantly decreased as compared to the level of malondialdehyde (623+/-22 nmol/g wet tissue) and reduced glutathione (226.6+/-19 microg/wet tissue) in the vehicle-treated group. The present study indicates that melatonin has a neuroprotective action in focal ischemia, which may be attributed to its antioxidant property.
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PMID:Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rats. 1167 35

Melatonin was found to be a potent free radical scavenger in 1993. Since then over 800 publications have directly or indirectly confirmed this observation. Melatonin scavenges a variety of reactive oxygen and nitrogen species including hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide and peroxynitrite anion. Based on the analyses of structure-activity relationships, the indole moiety of the melatonin molecule is the reactive center of interaction with oxidants due to its high resonance stability and very low activation energy barrier towards the free radical reactions. However, the methoxy and amide side chains also contribute significantly to melatonin's antioxidant capacity. The N-C=O structure in the C3 amide side chain is the functional group. The carbonyl group in the structure of N-C=O is key for melatonin to scavenge the second reactive species and the nitrogen in the N-C=O structure is necessary for melatonin to form the new five membered ring after melatonin's interaction with a reactive species. The methoxy group in C5 appears to keep melatonin from exhibiting prooxidative activity. If the methoxy group is replaced by a hydroxyl group, under some in vitro conditions, the antioxidant capacity of this molecule may be enhanced. However, the cost of this change are decreased lipophility and increased prooxidative potential. Therefore, in in vivo studies the antioxidant efficacy of melatonin appears to be superior to its hydroxylated counterpart. The mechanisms of melatonin's interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through an radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4 and C7 and nitrosation. Melatonin also has the ability to repair damaged biomolecules as shown by the fact that it converts the guanosine radical to guanosine by electron transfer. Unlike the classical antioxidants, melatonin is devoid of prooxidative activity and all known intermediates generated by the interaction of melatonin with reactive species are also free radical scavengers. This phenomenon is defined as the free radical scavenging cascade reaction of the melatonin family. Due to this cascade, one melatonin molecule has the potential to scavenge up to 4 or more reactive species. This makes melatonin very effective as an antioxidant. Under in vivo conditions, melatonin is often several times more potent than vitamin C and E in protecting tissues from oxidative injury when compared at an equivalent dosage (micromol/kg). Future research in the field of melatonin as a free radical scavenger might be focused on: 1), signal transduction and antioxidant enzyme gene expression induced by melatonin and its metabolites, 2), melatonin levels in tissues and in cells, 3), melatonin structure modifications, 4), melatonin and its metabolites in plants and, 5), clinical trials using melatonin to treat free radical related diseases such as Alzheimer's, Parkinson's, stroke and heart disease.
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PMID:Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. 1189

Mixed efficacy of neuroprotective drugs in clinical trials has led to the emergence of the approach of combination therapy in stroke. The present study was carried out to investigate the effect of the combination of melatonin (potent antioxidant) and meloxicam (preferential inhibitor of cyclooxygenase-2 enzyme) against a middle cerebral artery occlusion model of stroke in rats. Male Wistar rats in the weight range of 250-300 g were used. Rats were anesthetized using chloral hydrate (400 mg/kg i.p) and subjected to 2 h of transient middle cerebral artery occlusion. Melatonin was administered at a dose of 20 mg/kg i.p. four times: at the time of middle cerebral artery occlusion, 1.5 h after middle cerebral artery occlusion, at the time of reperfusion, and 1 h after reperfusion. Meloxicam (2.5 mg/kg) was administered 4 h after middle cerebral artery occlusion. Motor performance tests (grip test, foot fault test, rotarod performance test, spontaneous locomotor activity), markers of oxidative stress, and triphenyltetrazolium chloride staining were carried out 24 h after middle cerebral artery occlusion. A vehicle-treated group was run in parallel. It was observed that melatonin treatment improved the motor performance and significantly attenuated the levels of malondialdehyde (MDA) as compared with the middle cerebral artery occluded group. Meloxicam treatment at the dose used neither showed significant improvement on the motor performance nor decreased the levels of MDA significantly as compared with the middle cerebral artery occluded group. However, when the combination of the two drugs was used, better protection was observed as was evident by the significant decrease in the percent foot fault errors, the increase in the time spent on the rotarod, and the increase in the six-point neurological score and grip test score. There was also a significant decrease in the levels of MDA in the combination group. The results of the present study demonstrate that enhanced protection is observed with the use of a combination of melatonin plus meloxicam in the middle cerebral artery occlusion model of acute ischemic stroke in rats.
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PMID:Enhanced protection by melatonin and meloxicam combination in a middle cerebral artery occlusion model of acute ischemic stroke in rat. 1199 Dec 32

Melatonin concentrations in serum, as well as urinary levels of its main metabolite, 6-sulphatoxymelatonin, decrease with age. In the course of aging, the frequency of heart diseases, both acute and chronic, systematically increases. The evidence from the last 10 years suggests that melatonin influences the cardiovascular system. The presence of vascular melatoninergic receptors/binding sites has been demonstrated; these receptors are functionally linked with vasoconstrictor or vasodilatory effects of melatonin. Melatonin can contribute in cardioprotection of the rat heart, following myocardial ischemia. It has been shown that patients with coronary heart disease have a low melatonin production rate, especially those with higher risk of cardiac infarction and/or sudden death. There are clinical data reporting some alterations of melatonin in human stroke and coronary heart disease. The suprachiasmatic nucleus and, possibly, the melatoninergic system may also modulate cardiovascular rhythmicity. Hypercholesterolemia and hypertension are the other age-related symptoms. People with high levels of LDL-cholesterol have low levels of melatonin. It has been shown that melatonin suppresses the formation of cholesterol by 38% and reduces LDL accumulation by 42%. A 10-20% reduction of cholesterol concentration in women using the B-oval pill has been observed. It is a very important because, even a 10-15% reduction in blood cholesterol concentration has bee shown to result in a 20 to 30% decrease in the risk of coronary heart disease. People with hypertension have lower melatonin levels than those with normal blood pressure. The administration of the hormone in question declines blood pressure to normal range. It has been observed that melatonin, even in a dose 1 mg, reduced blood pressure and decreased catecholamine level after 90 min in human subjects. Melatonin may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus; 2) as an antioxidant which lowers blood pressure; 3) by decreasing the level of catecholamines, or 4) by relaxing the smooth muscle in the aorta wall.
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PMID:Melatonin and the cardiovascular system. 1201 57

Reduction of cerebral edema, an early symptom of ischemia, is one of the most important remedies for reducing subsequent chronic neural damage in stroke. Melatonin, a metabolite of tryptophan released from the pineal gland, has been found to be effective against neurotoxicity in vitro. The present study was aimed to demonstrate the effectiveness of melatonin in vivo in reducing ischemia-induced edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.): just prior to 1 h MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. Increases in T2-weighted signals in ischemic sites of the brain were clearly observed after MCA occlusion. The signal increase was found mainly in the striatum and in the cerebral cortex in saline-treated control rats. In the melatonin-treated group, the total volume of cerebral edema was reduced by 45.3% compared to control group (P < 0.01). The protective effect of melatonin against cerebral edema was more clearly observed in the cerebral cortex (reduced by 56.1%, P < 0.01), while the reduction of edema volume in the striatum was weak (reduced by 23.0%). The present MRI study clearly demonstrated that melatonin is effective in reducing edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments.
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PMID:Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats. 1246 99

The antioxidant and anti-inflammatory effects of melatonin on kainic acid (KA)-induced neurodegeneration in the hippocampus were evaluated in vivo. It has been suggested that the pineal secretory product, melatonin, protects neurons in vitro from excitotoxicity mediated by kainate-sensitive glutamate receptors, and from oxidative stress-induced DNA damage and apoptosis. In this study, we injected 10 mg/kg kainate intraperitoneally (i.p.) into adult male Sprague-Dawley rats. This results in selective neuronal degeneration accompanied by intense microglial activation and triggers DNA damage in the hippocampus. We tested the in vivo efficacy of melatonin in preventing KA-induced neurodegeneration, oxidative stress and neuroinflammation in the hippocampus. Melatonin (2.5 mg/kg, i.p.) was given 20 min before, immediately after, and 1 and 2 hr after KA administration. Rats were killed 72 hr later and their hippocampi were examined for evidence of DNA damage (in situ dUTP end-labeling, i.e. TUNEL staining), cell viability (hematoxylin and eosin staining), and microglial (isolectin-B4 histochemistry) and astroglial responses (glial fibrillary acidic protein immunohistochemistry), as well as lipid peroxidation (4-hydroxynonenal immunohistochemistry). A cumulative dose of 10 mg/kg melatonin attenuates KA-induced neuronal death, lipid peroxidation, and microglial activation, and reduces the number of DNA breaks. A possible mechanism for melatonin-mediated neuroprotection involves its antioxidant and anti-inflammatory actions. The present data suggest that melatonin is potentially useful in the treatment of acute brain pathologies associated with oxidative stress-induced neuronal damage such as epilepsy, stroke, and traumatic brain injury.
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PMID:Melatonin attenuates kainic acid-induced hippocampal neurodegeneration and oxidative stress through microglial inhibition. 1256

Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that a single injection of melatonin before ischemia significantly reduced the infarct volume in both permanent and 3-hr middle cerebral artery occlusion (MCAO) rat stroke models. Nitric oxide (NO) and other free radicals play an important role in the pathogenesis of cerebral ischemia, and they have been postulated to mediate the breakdown of the blood-brain barrier (BBB) during ischemia. In this study, we evaluated the influence of melatonin, given at 30 min before MCAO, on brain NO concentration and BBB breakdown. Brain NO concentration was measured at 15 min of MCAO using electron paramagnetic resonance spectroscopy. BBB breakdown at 3 hr of reperfusion following 3 hr of MCAO was assessed using Evans blue extravasation. The relative brain NO concentration was increased to 141.69 +/- 9.71% (mean +/- S.E.M.; n = 9) at 15 min of MCAO. Treatment with melatonin at 1.5, 5, or 50 mg/kg significantly reduced the brain NO concentration to 104.20 +/- 11.20% (n = 8), 55.67 +/- 5.58% (n = 11), and 104.86 +/- 12.56% (n = 9), respectively. Melatonin at 5 mg/kg did not affect Evans blue extravasation. Our results suggest that a single injection of melatonin protects against focal cerebral ischemia partly via inhibition of ischemia-induced NO production and that this regimen does not prevent BBB breakdown following ischemia-reperfusion.
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PMID:Melatonin reduces nitric oxide level during ischemia but not blood-brain barrier breakdown during reperfusion in a rat middle cerebral artery occlusion stroke model. 1256 2


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