- Prenatal perturbation of brain circulation and oxygenation is a leading cause of perinatal brain damage affecting about 0.3–0.9% of births. Hypoxia-ischemia (HI) in preterm human infants at gestational week 23–32 results in neurodevelopmental abnormalities in childhood, presenting as learning disability, seizure activity, motor impairment and in the most severe cases, death. Here, we examined the potential of MgSO 4 treatment, prior to foetal hypoxia, to attenuate hypoxia induced damage in a murine model of maternal hypoxia. We studied the time course of maternal hypoxia and MgSO 4 pre-treatment effects on cerebellar tissue by means of DNA microarray analyses. Mild hypoxia induced minor expression changes in most genes. However, there were 5 gene sets which were down-regulated by maternal hypoxia. MgSO 4 pre-treatment abrogated these decreases in gene. A cell cycle gene set which responded immediately (2 h) to hypoxia, showed a delayed response (24 h) when MgSO 4 pre-treatment was given. Similar proportions of cell death were observed in all groups before P7, where combined hypoxia and MgSO 4 treatment increased cell death in the internal granule layer. There were a higher number of BrdU positive cells at the end of hypoxic episodes and a down-regulation of Reelin signaling, compared to control. MgSO 4 pre-treatment prevented the enhancement of cell proliferation due to hypoxia and increased Reelin levels. Altogether, MgSO 4 pre-treatment both reduced the number of genes differentially affected by hypoxia and delayed the responses to hypoxia. In addition, MgSO 4 pre-treatment modified the nature of the transcriptional response; while hypoxia induced down-regulation of gene sets, MgSO 4 pre-treatment mostly up-regulated them. The dual reaction to the MgSO 4 treatment may be the source of the ambiguity in observations reported for affected newborns.