Characterization of microglia in the rat subventricular zone after neonatal hypoxia-ischemia

Background
Recent findings indicate a regulatory role of microglia on neurogenesis in the subventricular zone (SVZ). SVZ microglia in the adult rat are sought to adopt a supportive phenotype after ischemic stroke. Early postnatal microglia are endogenously activated and may therefore express an increased sensitivity to neonatal hypoxia-ischemia (HI). Therefore, we sought to investigate the impact of HI on the microglial phenotype in the early postnatal SVZ.
Methods
Postnatal-day (P)7 rats underwent sham or right-hemispheric HI surgery. Microglia in the SVZ, the adjacent cortex and the corpus callosum were immunohistochemically analyzed at P10, P20 and P40. Further, the transcriptome of SVZ microglia isolated at P10 and P20 was analyzed. Lastly, the effect of P10 microglia on in vitro neurosphere generation was investigated.
Results
The SVZ microglial response upon HI, characterized by cellular accumulation, prolonged activation and phagocytosis, is SVZ-specific and does not occur in adjacent brain regions. At the transcriptomic level, SVZ microglia adopt a complex phenotype, that resembles neither the M1 or M2 polarization state, but instead shares commonly expressed genes with microglia in neurodegenerative diseases. Finally, SVZ microglia appear to show trophic support for neurosphere generation in vitro in a concentration dependent manner.
Conclusions
Microglia are an inherent cellular component of the early postnatal SVZ and undergo specific developmental changes that are disrupted by neonatal HI injury. The SVZ microglial response to HI is complex and beyond a simplified pro- or anti-inflammatory phenotype. Our findings represent a solid basis for future research on SVZ microglia.