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

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease that is associated with significant morbidity and mortality. There is substantial evidence to suggest that oxidative stress is significant in the development of acute brain injury following SAH. Melatonin is a strong antioxidant that has low toxicity and easily passes through the blood-brain barrier. Previous studies have shown that melatonin provides neuroprotection in animal models of ischemic stroke. This study hypothesizes that melatonin will provide neuroprotection when administered 2 hr after SAH. The filament perforation model of SAH was performed in male Sprague-Dawley rats weighing between 300 and 380 g. Melatonin (15 or 150 mg/kg), or vehicle was given via intraperitoneal injection 2 hr after SAH. Mortality and neurologic deficits were assessed 24 hr after SAH. A significant reduction in 24-hr mortality was seen following treatment with high dose melatonin. There was no improvement in neurologic scores with treatment. Brain water content and lipid peroxidation were measured following the administration of high dose melatonin to identify a mechanism for the increased survival. High dose melatonin tended to reduce brain water content following SAH, but had no effect on the lipid peroxidation of brain samples. Large doses of melatonin significantly reduces mortality and brain water content in rats following SAH through a mechanism unrelated to oxidative stress.
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PMID:Melatonin decreases mortality following severe subarachnoid hemorrhage. 1828 72

We have previously shown that melatonin reduces postischemic rises in the blood-brain barrier (BBB) permeability and improves neurovascular dysfunction and hemorrhagic transformation following ischemic stroke. It is known that activation of the matrix metalloproteinases (MMPs) plays a crucial role in the pathogenesis of brain edema and hemorrhagic transformation after ischemic stroke. We, herein, investigated whether melatonin would ameliorate MMP-2 and MMP-9 activation and expression in a rat model of transient focal cerebral ischemia. Adult male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery (MCA) occlusion using an intraluminal filament. Melatonin (5 mg/kg) or vehicle was intravenously injected upon reperfusion. Brain infarction and hemorrhage within infarcts were measured, and neurological deficits were scored. The activity and expression of MMP-2 and MMP-9 were determined by zymography, in situ zymography and Western immunoblot analysis. Cerebral ischemia-reperfusion induced increased pro-MMP-9 and MMP-9 activity and expression 24 hr after reperfusion onset. Relative to controls, melatonin-treated animals, however, had significantly reduced levels in the MMP-9 activity and expression (P < 0.01), in addition to reduced brain infarct volume and hemorrhagic transformation as well as improved sensorimotor neurobehavioral outcomes. No significant change in MMP-2 activity was observed throughout the course experiments. Our results indicate that the melatonin-mediated reductions in ischemic brain damage and reperfusion-induced hemorrhage are partly attributed to its ability to reduce postischemic MMP-9 activation and increased expression, and further support the fact that melatonin is a suitable as an add-on to thrombolytic therapy for ischemic stroke patients.
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PMID:Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats. 1862 55

Melatonin is produced in the human pineal gland, particularly at night, with the circadian rhythm of blood melatonin levels closely paralleling its production within the pineal gland. Light exposure at night, or rapid transmeridian travel severely compromises the circadian production of melatonin. The disturbed melatonin rhythm contributes to jet lag and sleep inefficiency, both of which are improved by melatonin administration. Melatonin is also a highly effective direct free radical scavenger and antioxidant. In this capacity, melatonin reduces experimental cataractogenesis, traumatic injury to the spinal cord and brain, and protects against oxidative damage to neurons and glia in models of stroke, Parkinsonism, and Alzheimer's disease. Additionally, melatonin and its metabolites are highly effective in protecting against ionizing radiation. Finally, melatonin may be a treatment for hypertension. Melatonin's high efficacy, its high safety profile, and its virtual lack of toxicity make it of interest in clinical medicine.
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PMID:Clinical aspects of melatonin. 1899 97

Oxidative stress is implicated in the pathogenesis of a number of neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis and stroke in the adult as well as in conditions such as periventricular white matter damage in the neonatal brain. It has also been linked to the disruption of blood brain barrier (BBB) in hypoxic-ischemic injury. Both experimental and clinical results have shown that antioxidants such as melatonin, a neurohormone synthesized and secreted by the pineal gland and edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a newly developed drug, are effective in reducing oxidative stress and are promising neuroprotectants in reducing brain damage. Indeed, the neuroprotective effects of melatonin in many central nervous system (CNS) disease conditions such as amyotrophic lateral sclerosis, PD, AD, ischemic injury, neuropsychiatric disorders and head injury are well documented. Melatonin affords protection to the BBB in hypoxic conditions by suppressing the production of vascular endothelial growth factor and nitric oxide which are known to increase vascular permeability. The protective effects of melatonin against hypoxic damage have also been demonstrated in newborn animals whereby it attenuated damage in different areas of the brain. Furthermore, exogenous administration of melatonin in newborn animals effectively enhanced the surface receptors and antigens on the macrophages/microglia in the CNS indicating its immunoregulatory actions. Edaravone has been shown to reduce oxidative stress, edema, infarct volume, inflammation and apoptosis following ischemic injury of the brain in the adult as well as decrease free radical production in the neonatal brain following hypoxic-ischemic insult. It can counteract toxicity from activated microglia. This review summarizes the clinical and experimental data highlighting the therapeutic potential of melatonin and edaravone in neuroprotection in various disorders of the CNS.
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PMID:Antioxidants and neuroprotection in the adult and developing central nervous system. 1907 54

Melatonin's neuroprotective action has been demonstrated in experimental models of brain ischaemia. The relationship between stroke and melatonin levels has been based on scarce and small sample size studies. In addition, the changes have not been correlated with the age of patients. We compared levels of nocturnal urinary melatonin and its metabolite, 6-sulfatoxymelatonin (aMT6S) in a large series of acute ischaemic stroke patients and healthy volunteers. Consecutive ischaemic stroke patients with a first episode of anterior circulation stroke were recruited. Urine samples were collected in 127 patients on day 1 poststroke and in a control population including 216 healthy volunteers, from 20:00 to 08:00 hr. Melatonin and aMT6S were measured by radioimmunoassay. Differences in melatonin and aMT6S levels between ischaemic stroke patients and healthy volunteers were assessed by gender and age categories, using the Student's t-test. Melatonin excretion was decreased in stroke patients compared with healthy volunteers (74.1 +/- 13.9 versus 211.9 +/- 31.0 ng/hr; P = 0.0004), whereas aMT6S level was not significantly reduced (6371 +/- 1028 versus 4469 +/- 508 ng/hr; P = 0.10). Conversely, the stratification by age showed a significant reduction of both melatonin and aMT6S levels among ischaemic stroke patients over 70 yr (P = 0.001 and P = 0.03 respectively). The impact of melatonin at the acute stage of stroke on clinical severity and lesion size needs further assessment, as melatonin may have potential neuroprotective effects.
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PMID:Nocturnal urine melatonin and 6-sulphatoxymelatonin excretion at the acute stage of ischaemic stroke. 1931 98

Grapevine (Vitis vinifera) products, grape and grape juice, represent a valuable source of bioactive phytochemicals, synthesized by three secondary metabolic pathways (phenylpropanoid, isoprenoid and alkaloid biosynthetic routes) and stored in different plant tissues. In the last decades, compelling evidence suggested that regular consumption of these products may contribute to reducing the incidence of chronic illnesses, such as cancer, cardiovascular diseases, ischemic stroke, neurodegenerative disorders and aging, in a context of the Mediterranean dietary tradition. The health benefits arising from grape product intake can be ascribed to the potpourri of biologically active chemicals occurring in grapes. Among them, the recently discovered presence of melatonin adds a new element to the already complex grape chemistry. Melatonin, and its possible synergistic action with the great variety of polyphenols, contributes to further explaining the observed health benefits associated with regular grape product consumption.
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PMID:Bioactivity of grape chemicals for human health. 1944 14

Melatonin (n-acetyl-5-methoxy-tryptamine), a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia) is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood-brain barrier (BBB). Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.
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PMID:Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages. 1955 10

Synapto-dendritic dysfunction and rearrangement takes place over time at the peri-infarct brain after stroke, and the event plays an important role in post-stroke functional recovery. Here, we evaluated whether melatonin would modulate the synapto-dendritic plasticity after stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Local cerebral blood perfusion, somatosensory electrophysiological recordings and neurobehavioral tests were serially measured. Animals were sacrificed at 7 days after tMCAO. The brain was processed for Nissl-stained histology, Golgi-Cox-impregnated sections, or Western blotting for presynaptic proteins, synaptosomal-associated protein of 25 kDa (SNAP-25) and synaptophysin (a calcium-binding protein found on presynaptic vesicle membranes). Relative to controls, melatonin-treated animals had significantly reduced infarction volumes (P < 0.05) and improved neurobehavioral outcomes, as accessed by sensorimotor and rota-rod motor performance tests (P < 0.05, respectively). Melatonin also significantly improved the SNAP-25, but not synaptophysin, protein expression in the ischemic brain (P < 0.05). Moreover, melatonin significantly improved the dendritic spine density and the somatosensory electrophysiological field potentials both in the ischemic brain and the contralateral homotopic intact brain (P < 0.05, respectively). Together, melatonin not only effectively attenuated the loss of presynaptic protein, SANP-25, and dendritic spine density in the ischemic territory, but also improved the reductions in the dendritic spine density in the contralateral intact brain. This synapto-dendritic plasticity may partly account for the melatonin-mediated improvements in functional and electrophysiological circuitry after stroke.
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PMID:Melatonin improves presynaptic protein, SNAP-25, expression and dendritic spine density and enhances functional and electrophysiological recovery following transient focal cerebral ischemia in rats. 1970 97

Melatonin plays a neuroprotective role in models of neurodegenerative diseases. However, the molecular mechanisms underlying neuroprotection by melatonin are not well understood. Apoptotic cell death in the central nervous system is a feature of neurodegenerative diseases. The intrinsic and extrinsic apoptotic pathways and the antiapoptotic survival signal pathways play critical roles in neurodegeneration. This review summarizes the reports to date showing inhibition by melatonin of the intrinsic apoptotic pathways in neurodegenerative diseases including stroke, Alzheimer disease, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis. Furthermore, the activation of survival signal pathways by melatonin in neurodegenerative diseases is discussed.
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PMID:The antiapoptotic activity of melatonin in neurodegenerative diseases. 1981 70

We have shown that melatonin attenuated matrix metalloproteinase-9 (MMP-9) activation and decreased the risk of hemorrhagic transformation following cerebral ischemia-reperfusion. Herein, we investigate the possible involvement of the plasminogen/plasmin system and endogenous MMPs inhibitor underlying the melatonin-mediated MMP-9 inhibition. Mice were subjected to 1-hr ischemia and 48-hr reperfusion of the right middle cerebral artery. Melatonin (5 mg/kg) or vehicle was intravenously injected upon reperfusion. Brain infarction and hemorrhagic transformation were measured. Extracellular matrix damage was determined by Western immunoblot analysis for laminin protein. The activity and expression of MMP-2 and MMP-9 were determined by gelatin zymography, in situ zymography, and Western immunoblot analysis. In addition, the activities of tissue and urokinase plasminogen activators (tPA and uPA) were evaluated by plasminogen-dependent casein zymography. Endogenous plasminogen activator inhibitor (PAI) and tissue inhibitors of MMP (TIMP-1) were investigated using enzyme-linked immunosorbent assay (ELISA) and Western immunoblot analysis, respectively. Cerebral ischemia-reperfusion induced increased MMP-9 activity and expression at 12-48 hr after reperfusion onset. Relative to controls, melatonin-treated animals had significantly decreased MMP-9 activity and expression (P<0.05), in addition to reduced brain infarction and hemorrhagic transformation as well as improved laminin protein preservation. This melatonin-mediated MMP-9 inhibition was accompanied by reduced uPA activity (P<0.05), as well as increased TIMP-1 expression and PAI activity (P<0.05, respectively). These results demonstrate the melatonin's pluripotent mechanisms for attenuating postischemic MMP-9 activation and neurovascular damage, and further support it as an add-on to thrombolytic therapy for ischemic stroke patients.
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PMID:Melatonin inhibits postischemic matrix metalloproteinase-9 (MMP-9) activation via dual modulation of plasminogen/plasmin system and endogenous MMP inhibitor in mice subjected to transient focal cerebral ischemia. 2066 46


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