FETAL BRAIN INJURY FOLLOWING PROLONGED HYPOXEMIA AND PLACENTAL INSUFFICIENCY - A REVIEW

It is well established that severe, acute episodes of hypoxemia can da mage the brain before birth, but the effects of more sustained hypoxem ia are less well understood. We have used fetal sheep in a series of s tudies aimed at determining the effects of prolonged hypoxemia, induce d by placental insufficiency of differing severity and duration, on fe tal brain structure. Restriction of placental, and hence fetal, growth by carunclectomy caused impaired development of neural processes and connections in the hippocampus, cerebellum, and visual cortex; neurona l migration and neuronal numbers did not appear to be affected. Twenty days of placental insufficiency during late gestation induced by umbi licoplacental embolisation also caused abnormalities in brain structur e; the cerebellum, which develops late in gestation, was particularly affected. In the cortex, there was evidence of white matter lesions, a n increase in the size of capillaries and a proliferation of astroglia . We also examined the effects of shorter periods of hypoxemia (6-12 k r) near mid-gestation on brain structure; fetuses were allowed to reco ver for 7 or 35 days after the hypoxemic challenge. The major changes were mild focal damage in the cortical white matter, a reduction in th e number of Purkinje cells, a delay in the growth of neural processes in the cerebellum and proliferation of blood vessels. The hippocampus was also affected, in particular the areal density of pyramidal cells was reduced. The use of several classes of pharmacological agents with the potential to protect neurons from hypoxemic injury is discussed i n relation to the developing brain. (C) 1998 Elsevier Science Inc.