Effects of oxygen-glucose deprivation on microglial mobility and viability in developing mouse hippocampal tissues.

As brain-resident immune cells, microglia (MG) survey the brain parenchyma to maintain homeostasis during development and following injury. Recent work in perinatal stroke, a leading cause of lifelong disability, has implicated MG as targets for therapeutic intervention during stroke progression. Although MG responses are complex, work in developing rodents suggests that MG limit brain damage and promote recovery after stroke. However, little is known about how energy-limiting conditions affect MG survival and mobility in developing brain tissues. Here, we used confocal time-lapse imaging to monitor MG viability and motility during hypoxia or oxygen-glucose deprivation (OGD) in neonatal hippocampal tissue slices derived from GFP-reporter mice (CX3CR1GFP/+). We found that MG in P5-P7 neonatal tissues remain viable for at least 6hr of hypoxia but begin to die after 2hr of OGD. Both hypoxia and OGD reduced MG motility. Unexpectedly, some MG retain or recover motility during OGD, and these active MG can contact and engulf dead cells. MG from younger neonates (P2-P3) are more resistant to OGD than those from older ones, indicating increasing vulnerability with developmental age. Finally, we show that transient (2hr) OGD reduces MG motility, migration, and viability. Although MG motility is rapidly restored after transient OGD, it remains below control levels for many hours. Together, these results show that MG in neonatal mouse brain tissues are vulnerable to both transient and sustained OGD, and many MG die within hours after onset of OGD. Preventing MG death may, therefore, provide a strategy for promoting tissue restoration after stroke.