Pathogenic role of NAMPT in the perivascular regions after ischemic stroke in mice with type 2 diabetes mellitus.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0370712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2430 (Electronic) Linking ISSN: 00144886 NLM ISO Abbreviation: Exp Neurol Subsets: MEDLINE
    • Publication Information:
      Publication: Orlando Fl : Academic Press
      Original Publication: New York.
    • Subject Terms:
      Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/metabolism ; Ischemic Stroke* ; Stroke*/complications ; Stroke*/pathology; Animals ; Humans ; Mice ; Cytokines ; Glucose/metabolism ; Infarction, Middle Cerebral Artery/complications ; Nicotinamide Phosphoribosyltransferase/metabolism
    • Abstract:
      Ischemic stroke in patients with abnormal glucose tolerance results in poor outcomes. Nicotinamide phosphoribosyltransferase (NAMPT), an adipocytokine, exerts neuroprotective effects. However, the pathophysiological role of NAMPT after ischemic stroke with diabetes and the relationship of NAMPT with cerebrovascular lesions are unclear. The purpose of this study was to clarify the pathophysiological role of NAMPT in cerebral ischemia with diabetes, using db/db mice as a type 2 diabetes animal model. The number of degenerating neurons increased after middle cerebral artery occlusion and reperfusion (MCAO/R) in db/db mice compared with the degenerating neurons in db/+ mice. Extracellular NAMPT (eNAMPT) levels, especially monomeric eNAMPT, increased significantly in db/db MCAO/R mice but not db/+ mice in isolated brain microvessels. The increased eNAMPT levels were associated with increased expression of inflammatory cytokine mRNA. Immunohistochemical analysis demonstrated that NAMPT colocalized with GFAP-positive cells after MCAO/R. In addition, both dimeric and monomeric eNAMPT levels increased in the conditioned medium of primary cortical astrocytes under high glucose conditions subsequent oxygen/glucose deprivation. Our findings are the first to demonstrate the ability of increased monomeric eNAMPT to induce inflammatory responses in brain microvessels, which may be located near astrocyte foot processes.
      Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No potential conflicts of interest relevant to this article were reported.
      (Copyright © 2023 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Astrocytes; Diabetes; Ischemic stroke; Microvessel; NAMPT
    • Accession Number:
      0 (Cytokines)
      IY9XDZ35W2 (Glucose)
      EC 2.4.2.12 (Nicotinamide Phosphoribosyltransferase)
      EC 2.4.2.12 (nicotinamide phosphoribosyltransferase, mouse)
    • Publication Date:
      Date Created: 20231026 Date Completed: 20231221 Latest Revision: 20240121
    • Publication Date:
      20240121
    • Accession Number:
      10.1016/j.expneurol.2023.114584
    • Accession Number:
      37884188