RESPONSES OF THE FETAL CEREBRAL VASCULATURE TO PRENATAL CYTOTOXIC BRAIN-DAMAGE

Prenatal exposure to the drug methylazoxy-methanol acetate (MAM Ac) ha s been commonly used as an experimental model of prenatal cytotoxic br ain damage. We have examined the effects of this prenatal brain damage on the development of vasculature in the fetal neocortex, because vas culature is likely to play an important role in fetal brain repair. Pr egnant 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 E21, th e rats were overdosed with pentobarbitone (100 mg/kg) and fetuses remo ved for paraffin embedding, lectin histochemistry, and electron micros copy. For lectin histochemistry, sections were exposed to a horseradis h peroxidase-conjugated B4 isolectin from Griffonia simplicifolia. Fet uses 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 w ere no differences in growing tip density, capillary internal diameter , or stem vessel internal diameter. The only consistent differences be tween the two groups at the electron microscope level were an increase in vacuolisation and an irregular luminal surface in MAM Ac animals a t E15. Tight junction formation, basement membrane formation, and loss of fenestrations were not delayed in experimental animals. The result s indicate that there is no increase in angiogenic activity coincident with the fetal neocortical repair that follows MAM Ac induced damage.