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Published on: October 21, 2017
Effects of oxygen-glucose deprivation on microglial mobility and viability in developing mouse hippocampal tissues
1Department of Biology, University of Iowa, Iowa City, Iowa, USA.
Abstract:
As brain-resident immune cells, microglia (MG) survey the brain parenchyma to maintain homeostasis during development and following injury. Research in perinatal stroke, a leading cause of lifelong disability, has implicated MG as targets for therapeutic intervention during stroke. Although MG responses are complex, work in developing rodents suggests that MG limit brain damage after stroke. However, little is known about how energy-limiting conditions affect MG survival and mobility (motility and migration) in developing brain tissues. Here, we used confocal time-lapse imaging to monitor MG viability and mobility during hypoxia or oxygen-glucose deprivation (OGD) in hippocampal tissue slices derived from neonatal GFP-reporter mice (CX3CR1(GFP/+) ). We found that MG remain viable for at least 6 h of hypoxia but begin to die after 2 h of OGD, while both hypoxia and OGD reduce MG motility. Unexpectedly, some MG retain or recover motility during OGD and can engulf dead cells. Additionally, MG from younger neonates (P2-P3) are more resistant to OGD than those from older ones (P6-P7), indicating increasing vulnerability with developmental age. Finally, transient (2 h) OGD also increases MG death, and although 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.
Insights
Microglia (MG), crucial immune cells in the brain, are vulnerable to oxygen-glucose deprivation (OGD) during neonatal stroke. Their survival and motility decrease, highlighting a potential therapeutic target for stroke recovery.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia (MG) are brain-resident immune cells vital for homeostasis and injury response.
- Perinatal stroke research identifies MG as therapeutic targets, with evidence suggesting they limit brain damage in developing rodents.
- The impact of energy-limiting conditions on MG survival and mobility in developing brain tissue remains poorly understood.
Purpose of the Study:
- To investigate the effects of hypoxia and oxygen-glucose deprivation (OGD) on microglia viability and mobility in neonatal mouse hippocampal tissue.
- To determine the influence of developmental age on microglia's response to OGD.
- To assess the impact of transient OGD on microglia survival and motility.
Main Methods:
- Confocal time-lapse imaging was employed to monitor microglia (CX3CR1(GFP/+)) viability and mobility.
- Experiments were conducted on hippocampal tissue slices from neonatal mice under conditions of hypoxia or OGD.
- Microglia responses were analyzed in relation to developmental age (P2-P3 vs. P6-P7) and OGD duration (transient vs. sustained).
Main Results:
- Microglia remained viable for at least 6 hours under hypoxia but began dying after 2 hours of OGD.
- Both hypoxia and OGD significantly reduced microglia motility, though some cells retained or recovered motility and phagocytic capacity during OGD.
- Microglia from younger neonates (P2-P3) exhibited greater resistance to OGD than those from older neonates (P6-P7).
- Transient (2-hour) OGD also increased microglia death, with motility recovery being incomplete and prolonged.
Conclusions:
- Neonatal microglia in brain tissue are vulnerable to both transient and sustained OGD, with significant cell death occurring within hours.
- Microglia's vulnerability to OGD increases with developmental age.
- Preventing microglia death presents a potential therapeutic strategy for promoting tissue repair following neonatal stroke.

