Prenatal pathogenesis of hydro-micrencephaly induced by X-rays. An animal model.
Experimental results are presented which describe induction and pathogenesis of the hydro-micrencephaly in NMRI-mice after single X-irradiation with 0.9 Gy or 1.9 Gy on gestation day (gd) 12. The ultrastructural alterations in the ventricular walls are sequentially investigated up to gross developmental damage. The ventricular zone is the most sensitive region in the developing brain. Its constituting undifferentiated and proliferating cells lose their palisade like orientation and fail subsequently to differentiate into primitive neurons, glia cells, or ependymal cells. Structurally this results in the thinning of ventricular walls by more than 50% associated with periventricular oedema and a dilation of the brain ventricles by 20-60%. Damage is clearly more pronounced with the higher dose. Repair processes originate from regions with intact Zonulae adherents which give also rise to typical globular or cylindrical heterotopic structures; these are known as rosettes and made up from undifferentiated proliferating ventricular cells. Perinatally in these rosettes cell replication persists, at a time when cell production in the ventricular zone has ceased. Histological changes are most prominent in and around the telencephalic roof consisting in replacement of the ependymal lining by a felt of glial fibers, faulty myelinisation, and periventricular oedema; postnatally these structural alterations lead to hydro-micrencephaly. Results from this animal model can be translated to the human situation because the fundamental developmental processes in the brain of mammals are similar despite species related differences of the time scale.
Heinzmann
U
U
GSF-Forschungszentrum für Umwelt und Gesundheit, GmbH, Institut für Pathologie, Neuherberg, Federal Republic of Germany.
D000016:Abnormalities, Radiation-Induced / Q000209:etiology*; D000818:Animals; D004195:Disease Models, Animal; D005865:Gestational Age; D006130:Growth Disorders / Q000209:etiology; D006849:Hydrocephalus / Q000196:embryology / Q000209:etiology* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008815:Mice, Inbred Strains; D008831:Microcephaly / Q000196:embryology / Q000209:etiology* / Q000473:pathology; D008854:Microscopy, Electron; D011829:Radiation Dosage