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Effects of oxygen-glucose deprivation on microglial mobility and viability in developing mouse hippocampal tissues
Journal article   Open access   Peer reviewed

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

Ukpong Eyo and Michael E Dailey
Glia, Vol.60(11), pp.1747-1760
11/2012
DOI: 10.1002/glia.22394
PMCID: PMC3786781
PMID: 22847985

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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.
Neurons - pathology Hippocampus - pathology Cell Movement - physiology Hypoxia, Brain - pathology Hypoxia, Brain - physiopathology Glucose - deficiency Animals Microglia - physiology Cell Death - physiology Neurons - physiology Microglia - pathology Mice Hippocampus - physiopathology Cell Survival - physiology

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