Aggravated brain injury after neonatal hypoxic ischemia in microglia-depleted mice.

• TSUJI, Shunichiro

• DI MARTINO, Elena

• MUKAI, Takeo

• TSUJI, Shoko

• MURAKAMI, Takashi

• HARRIS, Robert A

• BLOMGREN, Klas

• ÅDEN, Ulrika

• 辻, 俊一郎

• 村上, 節

抄録

type:Journal Article

BACKGROUND:Neuroinflammation plays an important role in neonatal hypoxic-ischemic encephalopathy (HIE). Although microglia are largely responsible for injury-induced inflammatory response, they play beneficial roles in both normal and disease states. However, the effects of microglial depletion on neonatal HIE remain unclear.

METHODS:Tamoxifen was administered to Cx3cr1CreER/+Rosa26DTA/+ (microglia-depleted model) and Cx3cr1CreER/+Rosa26DTA/- (control) mice at P8 and P9 to assess the effect of microglial depletion. The density of microglia was quantified using Iba-1 staining. Moreover, the proportion of resident microglia after the HI insult was analyzed using flow cytometric analysis. At P10, the HI insult was conducted using the Rice-Vannucci procedure at P10. The infarct size and apoptotic cells were analyzed at P13. Cytokine analyses were performed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at P13.

RESULTS:At P10, tamoxifen administration induced > 99% microglial depletion in DTA+ mice. Following HI insult, there was persisted microglial depletion over 97% at P13. Compared to male DTA- mice, male DTA+ mice exhibited significantly larger infarct volumes; however, there were no significant differences among females. Moreover, compared to male DTA- mice, male DTA+ mice had a significantly higher density of TUNEL+ cells in the caudoputamen, cerebral cortex, and thalamus. Moreover, compared to female DTA- mice, female DTA+ mice showed a significantly greater number of TUNEL+ cells in the hippocampus and thalamus. Compared to DTA- mice, ELISA revealed significantly lower IL-10 and TGF-β levels in both male and female DTA+ mice under both normal conditions and after HI (more pronounced).

CONCLUSION:We established a microglial depletion model that aggravated neuronal damage and apoptosis after the HI insult, which was predominantly observed in males.

source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149909/

収録刊行物

• Journal of neuroinflammation

  Journal of neuroinflammation 17 (1), 111-, 2020-04-11

  BioMed Central

キーワード

• Hypoxic-ischemic encephalopathy
• Ischemic stroke
• Microglia
• Neonate

詳細情報

• CRID: 1050003824972949632
• NII論文ID: 120006841986
• ISSN: 17422094
• Web Site: http://hdl.handle.net/10422/00012660
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles