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Updated: May 14, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia activation in the extremely preterm human brain
Veena Supramaniam1, Regina Vontell, Latha Srinivasan
1Centre for the Developing Brain, Department of Perinatal Imaging and Health, Division of Imaging & Biomedical Engineering, The Rayne Institute, King's College London, St Thomas' Hospital, London, UK. veena.supramaniam@kcl.ac.uk
Background:
The periventricular white matter (PVWM) of the immature preterm brain is selectively vulnerable to a spectrum of injury. Although essential for normal brain development, the presence of resident microglia may exacerbate PVWM injury.
Methods:
We used immunohistochemistry to investigate microglia profile in human preterm noninjured control brains and in brains with evidence of germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH), with median gestational age (GA) of 24.1 and 25.4 wk, respectively.
Results:
The number of microglia in the PVWM was higher than the other brain regions in both the control and GMH/IVH groups. Microglial density increased further in the PVWM of GMH/IVH brains, regardless of hemorrhage severity and despite normal macroscopic and imaging appearances to the PVWM. This was due to an increase in activated Iba1/CD68- and not Iba/CD45-immunopositive microglia. However, there were very few CD68/Ki67 colocalized cells, suggesting that the source of this increase may be due to a quick transformation of CD45-immunopositive hematopoietic microglia into CD68-immunopositive microglia. There was also increased apoptosis in the PVWM of all cases of GMH/IVH, with axonal injury and increased tumor necrosis factor-α (TNF-α) expression evident in the most severe cases.
Conclusion:
Isolated GMH/IVH may influence ongoing brain development, with a significant role played by microglial activation.
Insights
Microglia activation in the periventricular white matter (PVWM) increases following germinal matrix/intraventricular hemorrhage (GMH/IVH) in preterm infants, impacting brain development. This suggests a significant role for microglial activation in PVWM injury.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- The immature preterm brain's periventricular white matter (PVWM) is susceptible to injury.
- Resident microglia, crucial for brain development, may worsen PVWM injury.
Purpose of the Study:
- To investigate microglial profiles in preterm brains with and without germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH).
Main Methods:
- Immunohistochemistry was used to examine microglia in control and GMH/IVH human preterm brains (median gestational age 24.1 and 25.4 weeks).
Main Results:
- Microglial numbers were higher in the PVWM of both groups, with increased density in GMH/IVH brains.
- Activated Iba1/CD68-positive microglia increased in GMH/IVH brains, suggesting rapid transformation of hematopoietic microglia.
- Apoptosis, axonal injury, and tumor necrosis factor-alpha (TNF-α) expression were elevated in GMH/IVH cases.
Conclusions:
- Germinal matrix/intraventricular hemorrhage (GMH/IVH) can affect preterm brain development.
- Microglial activation plays a significant role in the observed brain injury.
