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

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  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 9002991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1166 (Electronic) Linking ISSN: 08958696 NLM ISO Abbreviation: J Mol Neurosci Subsets: MEDLINE
    • Publication Information:
      Publication: Totowa, NJ : Humana Press
      Original Publication: Boston : Birkhäuser [i.e. Cambridge, MA : Birkhäuser Boston, c1989-
    • Subject Terms:
      Cell Adhesion*; Blood-Brain Barrier/*drug effects ; Endothelial Cells/*drug effects ; Excitatory Amino Acid Antagonists/*pharmacology ; Memantine/*pharmacology; Blood-Brain Barrier/cytology ; Blood-Brain Barrier/metabolism ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cells, Cultured ; Endothelial Cells/metabolism ; Endothelial Cells/physiology ; Humans ; Monocytes/drug effects ; Monocytes/metabolism ; Monocytes/physiology
    • Abstract:
      Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Our results show that memantine prevents the attachment of monocyte THP-1 cells to human brain microvascular endothelial cells (HBMVEs). An in vitro BBB model experiment displayed that memantine could rescue TNF-α-induced disruption of the in vitro BBB model. In addition, memantine also interferes with monocyte transmigration across the BBB model. Our results indicate that TNF-α significantly increased the expression of cell adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, which was prevented by pretreatment with memantine. Mechanistically, memantine reversed activation of the transcription factor NF-κB by preventing the phosphorylation and degradation of its inhibitor IκBα. Our data is the first to describe a novel anti-inflammatory mechanism driven by the endothelial cell-mediated neuroprotective effects of memantine.
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    • Contributed Indexing:
      Keywords: Alzheimer’s disease (AD); Blood-brain barrier (BBB); Endothelial cells; Memantine; NF-κB
    • Accession Number:
      0 (Cell Adhesion Molecules)
      0 (Excitatory Amino Acid Antagonists)
      W8O17SJF3T (Memantine)
    • Publication Date:
      Date Created: 20170422 Date Completed: 20180306 Latest Revision: 20181113
    • Publication Date:
      20221213
    • Accession Number:
      10.1007/s12031-017-0917-x
    • Accession Number:
      28429235