Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn piglet does not protect against cerebral damage

Transient perinatal hypoxia-ischemia (HI) can lead to delayed cerebral dama ge beginning 8-24 h after resuscitation. Cerebroprotective therapies applie d soon after HI may thus reduce the severity of brain injury. We have previ ously shown that MgSO4 administration to newborn piglets after HI fails to prevent the delayed global impairment in cerebral energy metabolism charact eristic of severe brain damage. However, high extracellular concentrations of magnesium ions have been found to prevent specific excitotoxic neural ce ll death in vivo and in vitro. This study therefore examined the hypothesis that MgSO4 administration after HI reduces damage in some regions of the b rain even though global energy metabolism is unaffected. Twelve newborn pig lets were subjected to global cerebral HI by transient occlusion of both co mmon carotid arteries and reduction of the inspired oxygen fraction to 0.12 until cerebral high-energy phosphates, measured by magnetic resonance spec troscopy, were significantly depleted. Subjects were randomly assigned to t wo groups of six: the first received MgSO4 (three doses, 400 mg/kg 1 h afte r resuscitation and 200 mg/kg at 12 and 24 h), and the second received plac ebo infusions. At 48 h after the start of the experiment, the piglets were killed and their brains were perfused, fixed, and embedded in paraffin wax. Five-micrometer sections were stained with hematoxylin and eosin to allow semiquantitative analysis of the severity and extent of injury to the hippo campus, cerebellum, cerebral cortex, caudate nucleus, thalamus, and striatu m and the white matter tracts. There was no difference in the severity of t issue damage between the MgSO4-treated group and the placebo-treated animal s in any brain region.