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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia in the human infant brain and factors that affect expression
Natalie Ambrose1, Michael Rodriguez2, Karen A Waters1,3
1Discipline of Medicine, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, NSW, 2006, Australia.
Abstract:
The present study reports on the microglial populations present in 34 regions of the human infant brain (1-11 months), and whether developmental parameters or extrinsic factors such as cigarette smoke exposure, prone sleeping and an upper respiratory tract infection (URTI) influence their expression. Further, we compare microglia populations amongst three sudden unexpected death in infancy (SUDI) sub-groups: explained SUDI (eSUDI, n = 7), sudden infant death syndrome (SIDS) I (n = 8) and SIDS II (n = 13). Ionised calcium binding adaptor molecule-1 (Iba1) was used to determine the morphology and area covered by microglia in a given brain region. Activation was explored using cluster-of-differentiation factor 68 (CD68) and human leukocyte antigen-DP,DQ,DR (HLA). We found regional heterogeneity in the area covered and activation status of microglia across the infant brain. The hippocampus, basal ganglia, white matter and dentate nucleus of the cerebellum showed larger areas of Iba1, while the brainstem had the smallest. Microglia in regions of the basal ganglia and cortex demonstrated positive correlations with infant developmental parameters, while in nuclei of the rostral medulla, negative correlations between microglia parameters were seen. URTI and cigarette smoke exposure were associated with a reduced microglial area in regions of the hippocampus and cortex (parietal and occipital), respectively. In the context of SIDS, a reduced microglial area was seen in SIDS II and fewer SIDS I infants demonstrated activated phenotypes in the hippocampus. Overall, we identify the distribution of microglia in the infant brain to be heterogenous, and influenced by intrinsic and extrinsic factors, and that the SIDS I group is a useful control group for future research into other infant CNS pathologies.
Insights
Microglia distribution in the infant brain is heterogeneous, influenced by development and external factors like smoke exposure. The SIDS I group serves as a control for infant brain research.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are crucial immune cells in the brain, with their role in infant brain development not fully understood.
- Understanding microglial heterogeneity is key to deciphering infant neurological conditions.
Purpose of the Study:
- To map microglial populations across 34 regions of the human infant brain (1-11 months).
- To investigate the influence of developmental parameters and extrinsic factors (cigarette smoke, prone sleeping, URTI) on microglial expression.
- To compare microglial populations among sudden unexpected death in infancy (SUDI) subgroups: explained SUDI (eSUDI), SIDS I, and SIDS II.
Main Methods:
- Immunohistochemistry using Ionised calcium binding adaptor molecule-1 (Iba1) for microglial morphology and area.
- Assessment of microglial activation using cluster-of-differentiation factor 68 (CD68) and human leukocyte antigen-DP,DQ,DR (HLA).
- Analysis of regional microglial heterogeneity and correlations with developmental and extrinsic factors.
Main Results:
- Significant regional differences in microglial area and activation were observed across the infant brain.
- The hippocampus, basal ganglia, white matter, and cerebellar dentate nucleus showed larger microglial areas compared to the brainstem.
- Positive correlations between microglia and developmental parameters were found in the basal ganglia and cortex, while URTI and smoke exposure were linked to reduced microglial area.
Conclusions:
- Microglial distribution in the infant brain is heterogeneous and influenced by both intrinsic developmental and extrinsic factors.
- Specific microglial alterations were noted in SIDS II and SIDS I subgroups, suggesting their potential role in SUDI.
- The SIDS I group shows promise as a control for future research on infant central nervous system pathologies.

