MgSO 4 reduces tertiary gliosis but does not improve EEG recovery, or white or grey matter cell survival after asphyxia in preterm fetal sheep.

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 randomly assigned to receive sham occlusion with saline infusion (n = 6), or i.v. infusions with MgSO 4 (n = 7) or vehicle (saline, n = 6) from 24 hours before hypoxia-ischaemia induced by umbilical cord occlusion, until 24 hours after occlusion. Sheep were killed after 21-days recovery, for 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 to vehicle+occlusion. Numbers of mature CC1+ oligodendrocytes were similarly reduced in both occlusion groups compared to sham occlusion. By 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. 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. MgSO 4 was associated with exacerbated loss of oligodendrocytes in the periventricular and intragyral white matter tracts, whereas mature, myelinating oligodendrocytes were similarly reduced in both occlusion groups. In the same regions, MgSO 4 was associated with an intermediate improvement in myelin density. Functionally, magnesium sulphate 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. Abstract figure legend Schematic summarising key study outcomes. In preterm fetal sheep exposed to hypoxia ischaemia (HI), a clinically comparable dose of 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. MgSO 4 was associated with exacerbated loss of oligodendrocytes in the periventricular and intragyral white matter tracts, whereas mature, myelinating oligodendrocytes were similarly reduced in both HI groups. In the same regions, MgSO 4 was associated with an intermediate improvement in myelin density. This article is protected by copyright. All rights reserved.