Microglia activation in the extremely preterm human brain

Veena Supramaniam, Regina Vontell, Latha Srinivasan, Josephine Wyatt-Ashmead, Henrik Hagberg, Mary Rutherford

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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- (TNF-) expression evident in the most severe cases.Conclusion:Isolated GMH/IVH may influence ongoing brain development, with a significant role played by microglial activation.

Original languageEnglish (US)
Pages (from-to)301-309
Number of pages9
JournalPediatric Research
Volume73
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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