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Updated: Aug 5, 2026
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Microglial maturation across human and mouse as a reference for interpreting large-animal models of perinatal brain
Isabelle K Shearer1, Adrienne Antonson2, Juliette Van Steenwinckel3
1School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, VIC, Australia.
Abstract:
Microglia play dynamic roles in the developing brain and are central mediators of injury responses in perinatal brain injury. In mice, microglial gene regulatory and transcriptional programes reveal progression through early, pre-mature and mature stages. In contrast, microglial maturation has not been systematically characterised in the large-brained species most widely used to model human perinatal brain injury, particularly sheep and pigs. These large-animal models are indispensable as they share gyrencephaly, an expanded subplate, and clinically relevant physiology with the human infant brain. Here, we integrate established mouse and human frameworks of microglial maturation with a critical re-analysis of available sheep and pig datasets to assess whether rodent-derived insights into microglial development extend to large-animal models. Current sheep datasets lack sufficient resolution to infer maturation states, whereas pig data, although limited, reveal stage-dependent patterns consistent with late-gestation human development. This review also briefly considers emerging data on microglial development in non-human primates and the extent to which microglial gene expression programes appear conserved across species. Overall, microglial transitions are most dynamic during fetal and early postnatal life, underscoring the importance of developmentally aligned benchmarks for interpreting injury responses and informing microglia-targeted neuroprotective strategies. IMPACT: This article provides the first structured comparison of microglial maturation across human and mouse and uses these frameworks to benchmark large-brain animal models of perinatal brain injury, addressing a key translational gap. It shows that while existing sheep datasets lack sufficient resolution to define microglial maturation states, available pig data align closely with human late-gestation microglial development, supporting their use for developmental benchmarking. The work highlights that failure to account for microglial developmental stage risks misinterpretation of injury responses and underscores the need for developmentally aligned microglial markers in large-animal and non-human primate models to guide microglia-targeted neuroprotective strategies.
Insights
Microglial development varies across species, with pig models showing promise for studying human perinatal brain injury. Understanding these differences is crucial for developing effective neuroprotective strategies.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia are key immune cells in the brain, with dynamic roles in development and injury.
- Mouse models show distinct microglial maturation stages, but this is less understood in large-brained species used for perinatal brain injury research.
- Large-brained animals like sheep and pigs are vital models due to shared brain structures and physiology with human infants.
Purpose of the Study:
- To compare microglial maturation across species, integrating mouse and human data.
- To assess the applicability of rodent-derived microglial development insights to large-animal models (sheep and pigs).
- To identify suitable animal models for studying human perinatal brain injury and informing neuroprotective strategies.
Main Methods:
- Integrated established mouse and human microglial maturation frameworks.
- Critically re-analyzed available sheep and pig microglial datasets.
- Considered emerging data from non-human primate microglial development.
Main Results:
- Sheep datasets lacked sufficient resolution to determine microglial maturation states.
- Pig datasets, though limited, indicated stage-dependent patterns aligning with late-gestation human development.
- Microglial transitions are most active during fetal and early postnatal periods across species.
Conclusions:
- Existing sheep datasets are insufficient for benchmarking microglial maturation.
- Pig models show potential for developmental benchmarking in perinatal brain injury research.
- Accounting for microglial developmental stage is essential for accurate injury response interpretation and developing targeted neuroprotective therapies.
