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Neonatal hypoxia-ischemia in rat elicits a region-specific neurotrophic response in SVZ microglia

Authors
  • Fisch, Urs1, 1
  • Brégère, Catherine1
  • Geier, Florian2, 3
  • Chicha, Laurie1
  • Guzman, Raphael1, 1, 2
  • 1 University Hospital Basel, University Basel, Basel, Switzerland , Basel (Switzerland)
  • 2 University Basel, Basel, Switzerland , Basel (Switzerland)
  • 3 Swiss Institute of Bioinformatics, Basel, Switzerland , Basel (Switzerland)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jan 18, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12974-020-1706-y
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundRecent findings describe microglia as modulators of neurogenesis in the subventricular zone (SVZ). SVZ microglia in the adult rat are thought to adopt a neurotrophic phenotype after ischemic stroke. Early postnatal microglia are endogenously activated and may therefore exhibit an increased sensitivity to neonatal hypoxia-ischemia (HI). The goal of this study was to investigate the impact of cortico-striatal HI on the microglial phenotype, function, and gene expression in the early postnatal SVZ.MethodsPostnatal day (P)7 rats underwent sham or right-hemispheric HI surgery. Microglia in the SVZ, the uninjured cortex, and corpus callosum were immunohistochemically analyzed at P10, P20, and P40. The transcriptome of microdissected SVZ and cortical microglia was analyzed at P10 and P20, and the effect of P10 SVZ microglia on neurosphere generation in vitro was studied.ResultsThe microglial response to HI was region-specific. In the SVZ, a microglial accumulation, prolonged activation and phagocytosis was noted that was not observed in the cortex and corpus callosum. The transcriptome of SVZ microglia and cortical microglia were distinct, and after HI, SVZ microglia concurrently upregulated pro- and anti-inflammatory as well as neurotrophic genes. In vitro, microglia isolated from the SVZ supported neurosphere generation in a concentration-dependent manner.ConclusionsMicroglia are an inherent cellular component of the early postnatal SVZ and undergo developmental changes that are affected on many aspects by neonatal HI injury. Our results demonstrate that early postnatal SVZ microglia are sensitive to HI injury and display a long-lasting region-specific response including neurotrophic features.

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