Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells

Jumnongprakhon, Pichaya; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

doi:10.1016/j.brainres.2016.05.049

Cited by 32 publications

(20 citation statements)

References 68 publications

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“…This likely prompted the group led by Govitrapong to test whether melatonin could ameliorate the effects of this drug on the brain . In in vitro studies, they have shown that melatonin reduces methamphetamine‐elicited autophagy, inflammation, and hippocampal progenitor cell death and conserves blood–brain barrier integrity of brain microvascular endothelial cells . They and others also have conducted in vivo studies and report that melatonin prevented the changes in neuronal nestin, doublecortin, and beta‐III tubulin in mice treated with methamphetamine (Fig.…”

Section: Melatonin As An Antioxidant: Waging War On Free Radicalsmentioning

confidence: 99%

Melatonin as an antioxidant: under promises but over delivers

Reíter

Mayo

Tan

et al. 2016

Journal of Pineal Research

1,261

1,104

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Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/ reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse.Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of agerelated diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule. K E Y W O R D Sdiseases of aging, drug toxicity, free radicals, ischemia/reperfusion, mitochondria-targeted antioxidant, organ transplantation, statins

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Section: Melatonin As An Antioxidant: Waging War On Free Radicalsmentioning

confidence: 99%

Melatonin as an antioxidant: under promises but over delivers

Reíter

Mayo

Tan

et al. 2016

Journal of Pineal Research

1,261

1,104

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“…Microvascular damage is reportedly reduced by MLT in response to brain hypoperfusion and reperfusion injury [32] , suggesting that MLT might exert a neuroprotective effect by protecting the microvessels themselves. Indeed there is evidence that MLT acts directly on vasculature to mediate blood flow to various vascular beds including the brain, to stabilize blood brain barrier integrity [33] , prevent endothelial cell dysfunction [34] , decrease nitric oxide and VEGF production, and suppress ischemia-induced cerebral edema [35] . Furthermore, neonatal treatment with oral MLT improves cerebral vascular function in chronically hypoxic newborn lambs by increasing cerebral blood flow and improving vascular function [36] .…”

Section: Discussionmentioning

confidence: 99%

Effects of Antenatal Melatonin Treatment on the Cerebral Vasculature in an Ovine Model of Fetal Growth Restriction

et al. 2017

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Chronic moderate hypoxia, such as occurs in fetal growth restriction (FGR) during gestation, compromises the blood-brain barrier (BBB) and results in structural abnormalities of the cerebral vasculature. We have previously determined the neuroprotective and antioxidant effects of maternal administration of melatonin (MLT) on growth-restricted newborn lambs. The potential of maternal MLT therapy for the treatment of cerebrovascular dysfunction-associated developmental hypoxia has also been demonstrated in newborn lambs. We assessed whether MLT had an effect on the previously reported structural and cerebral vascular abnormalities in chronically hypoxic FGR lambs. Single umbilical-artery ligation surgery was performed in fetuses at approximately 105 days of gestation (term: 147 days) to induce placental insufficiency and FGR, and treatment with either saline or an MLT infusion (0.1 mg/kg) was started 4 h after surgery. Ewes delivered naturally at term and lambs were euthanased 24 h later. We found a significant reduction in the number of laminin-positive blood vessels within the subcortical and periventricular white matter (SCWM and PVWM) and the subventricular zone (SVZ) in FGR (p < 0.0005) and FGR + MLT brains (p < 0.0005 vs. controls), with no difference found between FGR and FGR + MLT animals. This was associated with a significant decrease in VEGF immunoreactivity in FGR and FGR + MLT brains versus controls (p < 0.0005; SCWM and PVWM) and in the SVZ in FGR brains versus controls (p < 0.005) and also with significantly lower levels of proliferating blood vessels versus controls (p < 0.0005). Glucose transporter-1 immunoreactivity (vascular endothelium) was decreased in FGR versus control lambs (p < 0.0005) in SCWM, PVWM, and the SVZ; it was significantly increased in FGR + MLT lambs compared with FGR lambs in SCWM and PVWM (p < 0.005) and even more markedly in the SVZ (p < 0.0005). FGR brains showed a 72% reduction in pericyte coverage versus control lambs and 68% versus FGR + MLT in PVWM. In SCWM, we found a 77 and 73% reduction compared with control and FGR + MLT lambs, respectively, while in the SVZ, we observed a 68% reduction versus controls and a 70% reduction in FGR versus FGR + MLT lambs. Astrocyte end-feet coverage in the SCWM showed a significant 24% reduction in FGR versus control levels, a 42% decrease within the PVWM, and a 35% decrease within the SVZ versus controls. MLT normalized astrocyte attachment to blood vessels, with no difference seen between controls and FGR + MLT animals in any of the brain regions examined. We also observed a decrease in albumin extravasation and microhemorrhage in controls and FGR + MLT brains versus FGR lambs. Our results demonstrate that umbilicoplacental insufficiency is associated with FGR-produced vascular changes in the white matter and SVZ of FGR newborn brains and that maternal MLT prevented disruption of the BBB by protecting perivascular cells essential for the maintenance of vascular homeostasis and stability.

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“…Of note, melatonin shown protective effect against BBB damage induced by various stimuli, including transient focal cerebral ischemia in mice (Chen et al, 2006), excitotoxic injury in neonatal rats (Moretti et al, 2015) and methamphetamine-induced inflammation (Jumnongprakhon et al, 2016). Therefore, decreased levels of melatonin in old mice may contribute to the BBB disruption when facing various extrinsic or intrinsic stimuli because melatonin has demonstrated its protective effects against LPS-induced injury to the heart (Lu et al, 2015), brain (Carloni et al, 2016), lung (Lee et al, 2009) and liver (Wang et al, 2007) by scavenging a variety of free radicals (Manchester et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Melatonin has shown protective effect on BBB integrity via a variety of pathways: inhibition of the toll like receptor 4 (TLR4)/NF-κB signaling pathway in neonatal rats (Hu et al, 2017), inhibition of NADPH oxidase-2 (Jumnongprakhon et al, 2016), inhibition of MMP-9 (Alluri et al, 2016), inhibiton of AMP-activated protein kinase (AMPK) activation (Wang et al, 2017) and impact on silent information regulator 1 (SIRT1; Zhao et al, 2015) and NLRP3 inflammasome (Rahim et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

Melatonin Supplementation, a Strategy to Prevent Neurological Diseases through Maintaining Integrity of Blood Brain Barrier in Old People

Liu

Wang

Zhang

et al. 2017

Front. Aging Neurosci.

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Blood brain barrier (BBB) plays a crucial role in maintaining homeostasis of microenvironment that is essential to neural function of the central nervous system (CNS). When facing various extrinsic or intrinsic stimuli, BBB is damaged which is an early event in pathogenesis of a variety of neurological diseases in old patients including acute and chronic cerebral ischemia, Alzheimer’s disease and etc. Treatments that could maintain the integrity of BBB may prevent neurological diseases following various stimuli. Old people often face a common stress of sepsis, during which lipopolysaccharide (LPS) is released into circulation and the integrity of BBB is damaged. Of note, there is a significant decrease of melatonin level in old people and animal. Melatonin has been shown to preserves BBB integrity and permeability via a variety of pathways: inhibition of matrix metalloproteinase-9 (MMP-9), inhibition of NADPH oxidase-2, and impact on silent information regulator 1 (SIRT1) and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. More important, a recent study showed that melatonin supplementation alleviates LPS-induced BBB damage in old mice through activating AMP-activated protein kinase (AMPK) and inhibiting gp91phox, suggesting that melatonin supplementation may help prevent neurological diseases through maintaining the integrity of BBB in old people.

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Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells

Cited by 32 publications

References 68 publications

Melatonin as an antioxidant: under promises but over delivers

Melatonin as an antioxidant: under promises but over delivers

Effects of Antenatal Melatonin Treatment on the Cerebral Vasculature in an Ovine Model of Fetal Growth Restriction

Melatonin Supplementation, a Strategy to Prevent Neurological Diseases through Maintaining Integrity of Blood Brain Barrier in Old People

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