Blood–brain barrier dysfunction in mice induced by lipopolysaccharide is attenuated by dapsone

Zhou, Ting; Zhao, Lei; Zhan, Rui; He, Qihua; Tong, Yawei; Xia, Tian; Wang, Hecheng; Zhang, Tao; Fu, Yaoyun; Sun, Yang; Xu, Feng; Guo, Xiangyang; Fan, Dongsheng; Han, Hongbin; Chui, Dehua

doi:10.1016/j.bbrc.2014.09.093

Cited by 38 publications

(33 citation statements)

References 37 publications

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“…LPS has been shown to disrupt BBB in vitro (Zhao et al ., ) and in vivo (young mice) (Zhou et al ., ). However, its impact on the BBB of old mice remains unknown.…”

Section: Resultsmentioning

confidence: 97%

“…LPS has been shown to dose‐dependently increase BBB permeability (Nonaka et al ., ) and 1 mg kg −1 LPS compromised BBB integrity in young mice (Ruiz‐Valdepenas et al ., ; Zhou et al ., ). Unexpectedly, we found that only 1 mg kg −1 LPS significantly increased the extravasation of EB and IgG in old mice, suggesting that the BBB of old mice does not appear to be more vulnerable in response to LPS than young mice.…”

Section: Discussionmentioning

confidence: 97%

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Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice

et al. 2017

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SummaryBlood–brain barrier (BBB) dysfunction is considered to be an early event in the pathogenesis of a variety of neurological diseases in old patients, and this could occur in old people even when facing common stress. However, the mechanism remains to be defined. In this study, we tested the hypothesis that decreased melatonin levels may account for the BBB disruption in old mice challenged with lipopolysaccharide (LPS), which mimicked the common stress of sepsis. Mice (24–28 months of age) received melatonin (10 mg kg−1 day−1, intraperitoneally, i.p.) or saline for one week before exposing to LPS (1 mg kg−1, i.p.). Evan's blue dye (EB) and immunoglobulin G (IgG) leakage were used to assess BBB permeability. Immunostaining and Western blot were used to detect protein expression and distribution. Our results showed that LPS significantly increased BBB permeability in old mice accompanied by the degradation of tight junction proteins occludin and claudin‐5, suppressed AMP‐activated protein kinase (AMPK) activation, and elevated gp91phox protein expression. Interestingly, administration of melatonin for one week significantly decreased LPS‐induced BBB disruption, AMPK suppression, and gp91phox upregualtion. Moreover, activation of AMPK with metformin significantly inhibited LPS‐induced gp91phox upregualtion in endothelial cells. Taken together, our findings demonstrate that melatonin alleviates LPS‐induced BBB disruption through activating AMPK and inhibiting gp91phox upregulation in old mice.

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“…LPS has been shown to disrupt BBB in vitro (Zhao et al ., ) and in vivo (young mice) (Zhou et al ., ). However, its impact on the BBB of old mice remains unknown.…”

Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice

et al. 2017

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“…Worth of note, LPS has been shown to increase BBB permeability in vitro (Nonaka et al, 2004) and compromise BBB integrity in young (Ruiz-Valdepeñas et al, 2011; Zhou T. et al, 2014) and old mice (Wang et al, 2017). More interesting, LPS has been shown to induce BBB dysfunction via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived ROS (Liu et al, 2012; Zhao et al, 2014).…”

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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“…Dapsone inhibits myeloperoxidase, a mechanism that protects neurons. Moreover, dapsone is effective in Alzheimer's disease or stroke, a neurodegenerative disease caused by inflammation [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Recovery of Dementia Syndrome following Treatment of Brain Inflammation

Lee

Choi

Lee

et al. 2020

Dement Geriatr Cogn Disord Extra

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Aim/Background: This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer's disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer's disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain longterm period (usually within 2-3 years), brain cell inflammation can be demonstrated as the cause of dementia. Methods: This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from

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Blood–brain barrier dysfunction in mice induced by lipopolysaccharide is attenuated by dapsone

Cited by 38 publications

References 37 publications

Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice

Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice

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

Recovery of Dementia Syndrome following Treatment of Brain Inflammation

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