Magnesium sulphate reduces tertiary gliosis but does not improve EEG recovery or white or grey matter cell survival after asphyxia in preterm fetal sheep

Abstract

Abstract Maternal magnesium sulphate (MgSO 4 ) treatment is widely recommended before preterm birth for neuroprotection. However, this is controversial because there is limited evidence that MgSO 4 provides long‐term neuroprotection. Preterm fetal sheep (104 days gestation; term is 147 days) were assigned randomly to receive sham occlusion with saline infusion ( n = 6) or i.v. infusion with MgSO 4 ( n = 7) or vehicle (saline, n = 6) from 24 h before hypoxia–ischaemia induced by umbilical cord occlusion until 24 h after occlusion. Sheep were killed after 21 days of recovery, for fetal brain histology. Functionally, MgSO 4 did not improve long‐term EEG recovery. Histologically, in the premotor cortex and striatum, MgSO 4 infusion attenuated post‐occlusion astrocytosis (GFAP + ) and microgliosis but did not affect numbers of amoeboid microglia or improve neuronal survival. In the periventricular and intragyral white matter, MgSO 4 was associated with fewer total (Olig‐2 + ) oligodendrocytes compared with vehicle + occlusion. Numbers of mature (CC1 + ) oligodendrocytes were reduced to a similar extent in both occlusion groups compared with sham occlusion. In contrast, MgSO 4 was associated with an intermediate improvement in myelin density in the intragyral and periventricular white matter tracts. In conclusion, a clinically comparable dose of MgSO 4 was associated with moderate improvements in white and grey matter gliosis and myelin density but did not improve EEG maturation or neuronal or oligodendrocyte survival. image Key points Magnesium sulphate is widely recommended before preterm birth for neuroprotection; however, there is limited evidence that magnesium sulphate provides long‐term neuroprotection. In preterm fetal sheep exposed to hypoxia–ischaemia (HI), MgSO 4 was associated with attenuated astrocytosis and microgliosis in the premotor cortex and striatum but did not improve neuronal survival after recovery to term‐equivalent age, 21 days after HI. Magnesium sulphate was associated with loss of total oligodendrocytes in the periventricular and intragyral white matter tracts, whereas mature, myelinating oligodendrocytes were reduced to a similar extent in both occlusion groups. In the same regions, MgSO 4 was associated with an intermediate improvement in myelin density. Functionally, MgSO 4 did not improve long‐term recovery of EEG power, frequency or sleep stage cycling. A clinically comparable dose of MgSO 4 was associated with moderate improvements in white and grey matter gliosis and myelin density but did not improve EEG maturation or neuronal or oligodendrocyte survival.