Microglia activation in the extremely preterm human brain

作者:Supramaniam Veena*; Vontell Regina; Srinivasan Latha; Wyatt Ashmead Josephine; Hagberg Henrik; Rutherford Mary
来源:Pediatric Research, 2013, 73(3): 301-309.
DOI:10.1038/pr.2012.186

摘要

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 lba1/CD68-and not lba/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-alpha (TNF-alpha) expression evident in the most severe cases. CONCLUSION: Isolated GMH/IVH may influence ongoing brain development, with a significant role played by microglial activation.

  • 出版日期2013-3