Melatonin decreases neurovascular oxidative/nitrosative damage and protects against early increases in the blood–brain barrier permeability after transient focal cerebral ischemia in mice

Abstract

We have recently shown that melatonin decreases the late (24 hr) increase in blood–brain barrier (BBB) permeability and the risk of tissue plasminogen activator‐induced hemorrhagic transformation following ischemic stroke in mice. In the study, we further explored whether melatonin would reduce postischemic neurovascular oxidative/nitrosative damage and, therefore, improve preservation of the early increase in the BBB permeability at 4 hr after transient focal cerebral ischemia for 60 min in mice. Melatonin (5 mg/kg) or vehicle was given intraperitoneally at the beginning of reperfusion. Hydroethidine (HEt) in situ detection and immunohistochemistry for nitrotyrosine were used to evaluate postischemic accumulation in reactive oxygen and nitrogen species, respectively, in the ischemic neurovascular unit. BBB permeability was evaluated by spectrophotometric and microscopic quantitation of Evans Blue leakage. Relative to controls, melatonin‐treated animals not only had a significantly reduced superoxide accumulation in neurovascular units in boundary zones of infarction, by reducing 35% and 54% cytosolic oxidized HEt in intensity and cell‐expressing percentage, respectively (P < 0.001), but also exhibited a reduction in nitrotyrosine by 52% (P < 0.01). Additionally, melatonin‐treated animals had significantly reduced early postischemic disruption in the BBB permeability by 53% (P < 0.001). Thus, melatonin reduced postischemic oxidative/nitrosative damage to the ischemic neurovascular units and improved the preservation of BBB permeability at an early phase following transient focal cerebral ischemia in mice. The findings further highlight the ability of melatonin in anatomical and functional preservation for the ischemic neurovascular units and its relevant potential in the treatment of ischemic stroke.

Therapeutic Effect of Melatonin in Experimental Uveitis

“…In agreement, it was shown that melatonin attenuates the postischemic increase in bloodbrain barrier permeability following ischemic stroke in mice, 44 reduces cerebral edema, and decreases bloodbrain barrier permeability in rats. 45 In addition, it was demonstrated that melatonin protects endothelial barrier integrity and preserves microvascular blood perfusion after ischemia reperfusion in hamster cheek pouch.…”

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

“…Moreover, melatonin has demonstrated that it could protect BBB by ischemic and hemorrhagic stroke, and sepsis or inflammatory responses to infection (Chen et al, 2006;Reiter et al, 2010;Tocharus et al, 2010;Chern et al, 2012;Acuna-Castroviejo et al, 2014;Garcia et al, 2014;Wang et al, 2014aWang et al, , 2014bLacoste et al, 2015;Nguyen et al, 2015;Manchester et al, 2015;Zhao et al, 2015). According to its exerting effects, melatonin might be beneficial for protecting BBB in METH administration.…”

WITHDRAWN: Melatonin improves methamphetamine-induced blood brain barrier impairment through NADPH oxidase-2 in primary rat brain microvascular endothelium cells

“…Moreover, melatonin has demonstrated that it could protect BBB by ischemic and hemorrhagic stroke, and sepsis or inflammatory responses to infection (Chen et al, 2006;Reiter et al, 2010;Tocharus et al, 2010;Chern et al, 2012;Accuna-Castroviejo et al, 2014;Gracia et al, 2014;Locoste et al, 2015;Ngunen et al, 2015;Manchester et al, 2015;Zhao et al, 2015). According to its exerting effects, melatonin might be beneficial for protecting BBB in METH administration.…”