Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants.
Disabilities after brain injury in very preterm infants have mainly been attributed to noncystic periventricular white matter injury (PWMI). We analyzed spatiotemporal patterns of PWMI in the brains of 18 very preterm infants (25-29 postconceptional weeks [pcw]), 7 preterm infants (30-34 pcw), and 10 preterm controls without PWMI. In very preterm infants, we examined PWMI in detail in 2 axonal crossroad areas in the frontal lobe: C1 (lateral to the lateral angle of the anterior horn of the lateral ventricle, at the exit of the internal capsule radiations) and C2 (above the corpus callosum and dorsal angle of the anterior horn). These brains had greater microglia-macrophage densities and activation but lesser astroglial reaction (glial fibrillary acidic protein and monocarboxylate transporter 1 expression) than in preterm cases with PWMI. In preterm infants, scattered necrotic foci were rimmed by axonal spheroids and ionized calcium binding adaptor molecule 1-positive macrophages. Diffuse lesions near these foci consisted primarily of hypertrophic and reactive astrocytes associated with fewer microglia. No differences in Olig2-positive preoligodendrocytes between noncystic PWMI and control cases were found. These data show that the growing axonal crossroad areas are highly vulnerable to PWMI in very preterm infants and highlight differences in glial activation patterns between very preterm and preterm infants.
INSERM U676, Hôpital Robert Debré, 48 Blvd Sérurier, 75019 Paris, France. catherine.verney@inserm.fr
Catherine
C
Verney
Ivana
I
Pogledic
Valérie
V
Biran
Homa
H
Adle-Biassette
Catherine
C
Fallet-Bianco
Pierre
P
Gressens
D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D056784:Leukoencephalopathies / Q000209:etiology* / Q000473:pathology*; D007969:Leukomalacia, Periventricular / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D011247:Pregnancy; D047928:Premature Birth / Q000503:physiopathology*; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D000949:Histocompatibility Antigens Class II; D008840:Microfilament Proteins; D027501:Monocarboxylic Acid Transporters; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C112986:AIF1 protein, human; C405708:OLIG2 protein, human