title: Responses of the fetal cerebral vasculature to prenatal cytotoxic brain damage.
abstract: Prenatal exposure to the drug methylazoxy-methanol acetate (MAM Ac) has been commonly used as an experimental model of prenatal cytotoxic brain damage. We have examined the effects of this prenatal brain damage on the development of vasculature in the fetal neocortex, because vasculature is likely to play an important role in fetal brain repair. Pregnant Wistar strain rats received either MAM Ac (25 mg/kg) or saline on embryonic day (E) 13 by IP injection. At E15, E17, E19, and and E21, the rats were overdosed with pentobarbitone (100 mg/kg) and fetuses removed for paraffin embedding, lectin histochemistry, and electron microscopy. For lectin histochemistry, sections were exposed to a horseradish peroxidase-conjugated B4 isolectin from Griffonia simplicifolia. Fetuses exposed to MAM Ac showed significant deficits in cortical vessel branch point density at E15 and E17 (46% and 20%, respectively). There were also significant reductions in stem vessel density at these ages (34% and 26%, respectively) among MAM Ac exposed animals, but there were no differences in growing tip density, capillary internal diameter, or stem vessel internal diameter. The only consistent differences between the two groups at the electron microscope level were an increase in vacuolisation and an irregular luminal surface in MAM Ac animals at E15. Tight junction formation, basement membrane formation, and loss of fenestrations were not delayed in experimental animals. The results indicate that there is no increase in angiogenic activity coincident with the fetal neocortical repair that follows MAM Ac induced damage.
authors.affiliation: School of Anatomy, University of NSW, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Misztal
authors.forename: K W
authors.initials: KW
authors.lastname: Ashwell
authors.forename: L L
authors.initials: LL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000196:embryology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange; D008746:Methylazoxymethanol Acetate / Q000633:toxicity*; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D013723:Teratogens / Q000633:toxicity
chemical_list: D013723:Teratogens; D008746:Methylazoxymethanol Acetate