論文

国際誌
2023年10月24日

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

Experimental neurology
  • Yui Iwatani
  • ,
  • Hideki Hayashi
  • ,
  • Haruna Yamamoto
  • ,
  • Hayato Minamikawa
  • ,
  • Mitsuki Ichikawa
  • ,
  • Hayato Orikawa
  • ,
  • Aya Masuda
  • ,
  • Natsumi Tada
  • ,
  • Yoshiyuki Moriyama
  • ,
  • Norio Takagi

開始ページ
114584
終了ページ
114584
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.expneurol.2023.114584

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.

リンク情報
DOI
https://doi.org/10.1016/j.expneurol.2023.114584
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/37884188
ID情報
  • DOI : 10.1016/j.expneurol.2023.114584
  • PubMed ID : 37884188

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