- Fetal low brain oxygenation may be an outcome of maternal complications during pregnancy and is associated with increased risk of cerebral palsy and periventricular leukomalacia in newborns. One treatment used for prevention of fetal brain damage is maternal treatment with MgSO4. Although this treatment is indicated to reduce the risk of cerebral palsy in newborns, its use remains controversial. We have shown previously that pretreatment with MgSO4 in a mouse model of maternal hypoxia prevented a delay in the development of motor reflexes induced by hypoxia. We demonstrate here that pretreatment with MgSO4 reduces hypoxia-induced motor disabilities in adult offspring. This effect is associated with histologic protection of the Purkinje cells in the cerebellum and stabilization of brain-derived neurotrophic factor (BDNF) levels in the cerebellum. MgSO4 did not prevent the reduction in cerebral cortex cell density and cell size induced by maternal hypoxia, however, nor did it interfere with the modulation of BDNF and nerve growth factor (NGF) expression in the cerebral cortex. MgSO4 pretreatment also prevented the impairment of shortterm memory (30 min, P 0.05) but not long-term memory (7 days). Nevertheless, maternal pretreatment with MgSO4 reduced CA1 cell layer width and induced alterations in both NGF and BDNF in the hippocampus. These results support the prophylactic effect of MgSO4 against motor disabilities; however, they may also indicate possible harmful effects on the cerebral cortex and hippocampus. © 2004 Wiley-Liss, Inc.