Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

Wang, Fei; Zou, Zhirong; Gong, Yi; Dong, Yixin; Chen, Xun; Sun, Tao

doi:10.1007/s12031-017-0917-x

Cited by 36 publications

(21 citation statements)

References 30 publications

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“…Once activated, proinflammatory cytokine TNF-α increases expression of adhesion molecules (27). In a recent cell culture study investigating memantine, the authors reported that treating with memantine repressed TNF-α induced elevations of ICAM-1, VCAM-1, and E-selectin (28). Our data support the data of association between VCAM-1 and TNF-α in patients with AD.…”

Section: Discussionsupporting

confidence: 88%

Determination of adiponectin, tumor necrosis factor-alpha, and adhesion molecules in Azheimer’s disease

Savaş¹

2019

Erciyes Med J

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Objective: Though the data regarding the mechanisms behind neurodegeneration in addition to amyloid plaques and neurofibrillary tangles are not clear, there are emerging data for inflammation and microvascular changes to have contribution to the pathology of Alzheimer's disease (AD). The relationships between numerous biomarkers also need to be investigated. This study aimed to assess inflammatory marker tumor necrosis factor-alpha (TNF-α), adiponectin (a modulator of anti-inflammation), and potential microvascular markers for AD including both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in Turkish patients with AD and healthy elderly subjects, and the relationships among the variables in patients with AD. Materials and Methods: In this study, 46 patients with AD and 30 cognitively healthy controls over 60 years of age from the outpatient clinics of Ege University were included. Adiponectin, ICAM-1, VCAM-1, and TNF-α were evaluated by enzyme-linked immunosorbent assays. Results: The median adiponectin level in the AD group was higher than in the controls (p=0.002). Median VCAM-1, ICAM-1, and TNF-α values for patients with AD and the controls were similar. There were positive correlations between VCAM-1 and both TNF-α and adiponectin in the patients with AD (r=0.540, p<0.001, and r=0.301, p=0.044, respectively). Conclusion: Though a dramatic rise of adiponectin, and associations of VCAM-1 and both TNF-α and adiponectin in subjects with AD were shown, the clinical significances of these peripheral measurements need to be further investigated.

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Section: Discussionsupporting

confidence: 88%

Determination of adiponectin, tumor necrosis factor-alpha, and adhesion molecules in Azheimer’s disease

Savaş¹

2019

Erciyes Med J

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“…Importantly, KLF2 can maintain vascular barrier function by directly regulating the transcription of occludin . In addition, KLF2 decreased immune cell attachment and rolling on the endothelial monolayer by inhibiting the expression of adhesion molecules such as VCAM‐1 and E‐selectin . These observations suggest that memantine may have a wide range of pharmacological roles in maintaining normal endothelial functions.…”

Section: Discussionmentioning

confidence: 99%

Memantine protects against ischemia/reperfusion‐induced brain endothelial permeability

Liu

Huang

et al. 2018

IUBMB Life

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Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells. First, we found that memantine treatment prevented I/R-induced expression of tumor necrosis factor-α and interleukin-1β at both the mRNA and the protein levels. Additionally, our results indicate that memantine treatment significantly reduced endothelial monolayer permeability after I/R by increasing the expression of tight junction protein occludin and the adherens junction protein VE-cadherin. In addition, we found that memantine reduced the expression and activity of matrix metalloproteinase (MMP)-2 but not MMP-9 after I/R. Memantine also elevated the expression of tissue inhibitors of metalloproteinase-2. Mechanistically, we found that memantine increased the expression of the transcriptional factor Krueppel-like factor 2 (KFL2) through activating extracellular signal regulated kinase (ERK5). In conclusion, our results identified a novel function of memantine in maintaining brain vascular barrier function and suggested that memantine might be a potential therapeutic agent for the treatment of stroke. © 2018 IUBMB Life, 70(4):336-343, 2018.

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“…11 A recent study investigated that a novel neuroprotective mechanism of MEM on neurodegenerative disease, that pretreatment with low-dose MEM significantly prevents the attachment of monocyte to human brain microvascular endothelial cells (HBMECs) and ameliorates TNF-α induced disruption of BBB in vitro model. 37 However, little information regarding the roles of Accumulated evidence indicates that dysregulation or mutation of lncRNAs is tightly involved in diverse cellular process. 38 It is urgent to ascertain the dysregulated lncRNAs and the underlying mechanism in a variety of neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 99%

“…BBB permeability in AD microenvironment by up-regulating the expression of TJ-related proteins. A recent study investigated that a novel neuroprotective mechanism of MEM on neurodegenerative disease, that pretreatment with low-dose MEM significantly prevents the attachment of monocyte to human brain microvascular endothelial cells (HBMECs) and ameliorates TNF-α induced disruption of BBB in vitro model 37. A recent study investigated that a novel neuroprotective mechanism of MEM on neurodegenerative disease, that pretreatment with low-dose MEM significantly prevents the attachment of monocyte to human brain microvascular endothelial cells (HBMECs) and ameliorates TNF-α induced disruption of BBB in vitro model 37.…”

mentioning

confidence: 99%

The role of LINC00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis in Memantine mediated protective effects on blood‐brain barrier in AD microenvironment

Zhu

Miao

et al. 2019

J Cellular Molecular Medi

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The dysfunction of the blood‐brain barrier ( BBB ) is one of the main pathological features of Alzheimer's disease ( AD ). Memantine ( MEM ), an N ‐methyl‐ d ‐aspartate ( NMDA ) receptor antagonist, has been reported that been used widely for AD therapy. This study was performed to demonstrate the role of the MEM in regulating BBB permeability in AD microenvironment as well as its possible mechanisms. The present study showed that LINC 00094 was dramatically increased in Abeta 1‐42 ‐incubated microvascular endothelial cells ( EC s) of BBB model in vitro. Besides, it was decreased in MEM ‐incubated EC s. Silencing LINC 00094 significantly decreased BBB permeability, meanwhile up‐regulating the expression of ZO ‐1, occludin and claudin‐5. Furthermore, silencing LINC 00094 enhance the effect of MEM on decreasing BBB permeability in AD microenvironment. The analysis of the mechanism demonstrated that reduction of LINC 00094 inhibited Endophilin‐1 expression by up‐regulating miR‐224‐4p/miR‐497‐5p, promoted the expression of ZO ‐1, occludin and claudin‐5, and ultimately alleviated BBB permeability in AD microenvironment. Taken together, the present study suggests that the MEM / LINC 00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment. Silencing LINC 00094 combined with MEM provides a novel target for the therapy of AD .

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Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

Cited by 36 publications

References 30 publications

Determination of adiponectin, tumor necrosis factor-alpha, and adhesion molecules in Azheimer’s disease

Determination of adiponectin, tumor necrosis factor-alpha, and adhesion molecules in Azheimer’s disease

Memantine protects against ischemia/reperfusion‐induced brain endothelial permeability

The role of LINC00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis in Memantine mediated protective effects on blood‐brain barrier in AD microenvironment

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