Neuroprotective Effects by Magnesium Sulfate Pretreatment against Hypoxia-Ischemia in the Newborn Rat: Preliminary report

ABSTRACT

PURPOSE AND BACKGROUND: Recently several clinical studies suggested that maternal treatment with magnesium sulfate had protective effects against cerebral palsy in premature infants. But previous studies with differing perinatal animal models resulted in inconclusive results with regard to magnesium neuroprotection. Our purpose was to study the neuroprotective effect of magnesium sulfate and optimal dosage on hypoxicischemic brain damage in the newborn rat. METHOD: Seven-day-old rats(n=68) underwent right carotid ligation, followed by 3 hours of hypoxia(8% oxygen in 92% nitrogen). Rats received magnesium sulfate immediately before and again after hypoxia(two doses, 150mg-600mg/kg/dose, n=39), or saline solution(n=29). Severity of injury was assessed 5 days later, by visual evaluation of ipsilateral hemisphere infarction and by measurement of bilateral hemispheric cross sectional areas. RESULTS: Magnesium sulfate pre-treatment reduced the incidence of liquefactive cerebral infarction and atrophy from 80.8% in controls to 22.2% with magnesium sulfate(450 mg/kg/dose, P<0.05). Quantitation of hemispheric areas confirmed these findings. Percent protection based on inter-hemisphere area differences by pre-treatment with magnesium sulfate 450mg/kg/dose ranged from 71.1%(hippocampus) to 90.8%(striatum). However higher dose of magnesium(600mg/kg/dose) did not attenuate hypoxic-ischemic brain injury in the newborn rat but increased mortality. CONCLUSION: Pretreatment of magnesium sulfate has neuroprotective effects against hypoxia-ischemia in the newborn rat and adequate dose of magnesium sufate is important to protect the brain. Magnesium pretreatment may be an effective strategy to decrease the severity of neonatal hypoxic-ischemic brain injury in the adequate dose.