Maternal hypoxia during pregnancy induces fetal neurodevelopmental brain damage: Partial protection by magnesium sulfate

Abstract

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 MgSO(4). 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 MgSO(4) 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 MgSO(4) 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. MgSO(4) 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. MgSO(4) pretreatment also prevented the impairment of short-term memory (30 min, P < 0.05) but not long-term memory (7 days). Nevertheless, maternal pretreatment with MgSO(4) reduced CA1 cell layer width and induced alterations in both NGF and BDNF in the hippocampus. These results support the prophylactic effect of MgSO(4) against motor disabilities; however, they may also indicate possible harmful effects on the cerebral cortex and hippocampus.

Oligodendroglial Alterations and the Role of Microglia in White Matter Injury: Relevance to Schizophrenia

“…Such conditions can occur in association with maternal diabetes, asthma, anemia, or as a consequence of maternal or fetal heart disease [181, 182]. Premature or prolonged labor compromises fetal oxygenation, as the infant has not yet developed a fully functional cerebral blood supply and autoregulatory responses [183].…”

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

“…[7][8][9][10][11] If the observed associations between maternal asthma during pregnancy and offspring diseases are causal, there may be several potential underlying mechanisms explaining these links. 42 First, low maternal oxygen supply is related to restricted fetal oxygenation, 43 which has been associated with delays in the development of the nervous system, 44 adverse neurodevelopmental outcomes, 45 and impairment of vascular function 46 in animals. Moreover, maternal asthma during pregnancy has been shown to result in dysfunction of bronchial relaxation in offspring rats via inhibition of epinephrine synthesis.…”

Magnesium Sulfate Tocolysis and Intraventricular Hemorrhage in Very Preterm Infants

“…Damage to the endothelial cells and altered brain hemostasis [20] due to immaturity of the preterm infant's antioxidant system [21] and increased susceptibility to reactive oxygen species [22,23] that increases the risk for IVH, can be mitigated by an excess of magnesium (Mg) in the cerebro-spinal fluid (CSF). There is ample evidence that Mg increases the antioxidant properties and protects the brain cells from hypoxic injury [24,25] [26,27] and apoptosis [28], as well as normalizes platelet aggregation and adhesion [29]. Tocolytic MgSO 4 can be an additional resource for neonatal Mg because fetal Mg is dependent on maternal sources [30][31][32].…”