Hypoxemia near mid-gestation has long-term effects on fetal brain development

We rested the hypotheses that an episode of hypoxemia near mid-gestation in fetal sheep has long-term effects on brain development and that the extent and type of damage is related to the stage of development within a particu lar brain structure at the time of the hypoxemia. Fetal sheep (n = 8) were made hypoxemic at 90 +/- 2 days (term similar to 147 days) by restricting t he maternal blood supply to the placenta for 12 hours (h) using a vascular clamp so as to reduce fetal arterial O-2 saturation by 50%-60%. Fetuses wer e killed 35 days later and the brains analysed histologically and immunohis tochemically. Age-matched fetuses (n = 8) were used as controls. Gross brai n damage was observed in only I fetus, the most acidemic during the period of hypoxemia. There was a reduction of 12% (p < 0.05) in the cross-sectiona l area of the cerebral cortex in hypoxemic fetuses compared with controls. In lobule 6 of the cerebella of hypoxemic fetuses, significant reductions w ere seen in (a) the volume density of Purkinje cells (33%), (b) the width o f the molecular layer (13%), (c) the area of the inner granule cell layer ( 13%), (d) the area of the white matter (18%), and (e) the total cross-secti onal area (15%). There were also significant reductions in the area of arbo rization of Purkinje cell dendritic trees (50%), in the branching density ( 25%), and in the number of dendritic spines (31%). In the ventral hippocamp i of hypoxemic fetuses, there was a 36% reduction (p < 0.05) in the volume density of CA1 pyramidal cells and a 50% increase (p < 0.05%) in the number of astrocytes. We conclude that an episode of hypoxemia near mid-gestation reduces neuronal numbers in the hippocampus and cerebellum and probably al so in the cerebral cortex. The growth of neural processes in a particular r egion will be significantly retarded if the hypoxemia occurs at an early st age of the growth of neural processes (e.g. cerebellum) but not if developm ent is well advanced at the time of the insult (e.g. hippocampus). Damage i s sustained in the white matter of the cerebral hemispheres if the insult i s particularly seven. Together, these deficits could affect neural connecti vity and impair postnatal brain function.