Periventricular/intraventricular hemorrhage in neonatal mouse cerebrum.
Periventricular/intraventricular hemorrhage (PVH/IVH) into brain can occur in premature infants and is associated with poor developmental outcome. The purpose of this study was to develop and characterize a model of PVH/IVH in newborn mouse. We hypothesized that periventricular germinal matrix would exhibit reduced cell proliferation. PVH/IVH was induced in 1-day-old mice by injection of autologous blood into the periventricular tissue. Magnetic resonance images (MRI) were obtained from 15 minutes to 14 days later. Mice were killed 4 hours to 28 days later. Cell proliferation, dying cells, astrocyte and microglial reactions, neutrophils, and lymphocytes were quantified. Histological studies showed that MRI accurately localizes the hematoma but overestimates its size. The hematoma, located in the striatum and germinal tissue, always extended into the lateral ventricles. Cell proliferation, measured by Ki67 immunoreactivity, was suppressed bilaterally in germinal matrix and beyond from 8 hours to 7 days. Increased cell death was observed in the ipsilateral striatum and germinal matrix 1 and 2 days after PVH/IVH. Astrocyte and microglia reaction peaked at 2 days and persisted up to 28 days. Inflammatory response was minimal. Extravasated blood might play an important role in brain damage following PVH/IVH through suppression of cell proliferation.
Xue
Mengzhou
M
Department of Pathology, University of Manitoba, and Manitoba Institute of Child Health, Winnipeg, Canada.
Balasubramaniam
Janani
J
Buist
Richard J
RJ
Peeling
James
J
Del Bigio
Marc R
MR
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D001769:Blood; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D002452:Cell Count; D016923:Cell Death; D002455:Cell Division / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology*; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000378:metabolism; D007839:Functional Laterality; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D007249:Inflammation; D019394:Ki-67 Antigen / Q000378:metabolism; D007969:Leukomalacia, Periventricular / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009930:Organic Chemicals; D037121:Plant Lectins / Q000378:metabolism; D011247:Pregnancy; D013194:Staining and Labeling; D013997:Time Factors
D015703:Antigens, CD; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D009930:Organic Chemicals; D037121:Plant Lectins; C017707:Ricinus communis agglutinin-1; C435731:fluoro jade