Microglia activation in the extremely preterm human brain.
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.


CONCLUSIONS
Isolated GMH/IVH may influence ongoing brain development, with a significant role played by microglial activation.
Centre 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
Veena
V
Supramaniam
Regina
R
Vontell
Latha
L
Srinivasan
Josephine
J
Wyatt-Ashmead
Henrik
H
Hagberg
Mary
M
Rutherford
D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D002552:Cerebral Ventricles / Q000166:cytology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008131:London; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000502:physiology*; D008856:Microscopy, Fluorescence; D018709:Statistics, Nonparametric; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017493:Leukocyte Common Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C516769:PTPRC protein, human