Magnesium Sulfate Prevents Neurochemical and Long-Term Behavioral Consequences of Neonatal Excitotoxic Lesions: Comparison Between Male and Female Mice

J Neuropathol Exp Neurol. 2017 Oct 1;76(10):883-897. doi: 10.1093/jnen/nlx073.


Magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery is proposed as a neuroprotective strategy against neurological alterations such as cerebral palsy in newborns. However, long-term beneficial or adverse effects of MgSO4 and sex-specific sensitivity remain to be investigated. We conducted behavioral and neurochemical studies of MgSO4 effects in males and females, from the perinatal period to adolescence in a mouse model of cerebral neonatal lesion. The lesion was produced in 5-day-old (P5) pups by ibotenate intracortical injection. MgSO4 (600 mg/kg, i.p.) prior to ibotenate prevented lesion-induced sensorimotor alterations in both sexes at P6 and P7. The lesion increased glutamate level at P10 in the prefrontal cortex, which was prevented by MgSO4 in males. In neonatally lesioned adolescent mice, males exhibited more sequelae than females in motor and cognitive functions. In the perirhinal cortex of adolescent mice, the neonatal lesion induced an increase in vesicular glutamate transporter 1 density in males only, which was negatively correlated with cognitive scores. Long-term sequelae were prevented by neonatal MgSO4 administration. MgSO4 never induced short- or long-term deleterious effect on its own. These results also strongly suggest that sex-specific neuroprotection should be foreseen in preterm infants.

Keywords: Cognition; Development; Excitotoxic lesion; Magnesium sulfate; Prematurity; Sensorimotor behavior; Sex.

MeSH terms

  • Aging / drug effects
  • Animals
  • Animals, Newborn
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / pathology
  • Calcium Channel Blockers / administration & dosage*
  • Calcium Channel Blockers / blood
  • Disease Models, Animal
  • Excitatory Amino Acid Agonists / toxicity
  • Female
  • Functional Laterality
  • Gait Disorders, Neurologic / etiology
  • Gait Disorders, Neurologic / prevention & control*
  • Glutamic Acid / metabolism
  • Ibotenic Acid / toxicity
  • Longitudinal Studies
  • Magnesium Sulfate / administration & dosage*
  • Magnesium Sulfate / blood
  • Male
  • Mice
  • Motor Skills / drug effects
  • Neurotoxicity Syndromes / complications*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology
  • Sex Factors
  • Vesicular Glutamate Transport Protein 1 / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Calcium Channel Blockers
  • Excitatory Amino Acid Agonists
  • Vesicular Glutamate Transport Protein 1
  • Ibotenic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Magnesium Sulfate