Neuroprotective effect of long-term MgSO4 administration after cerebral hypoxia-ischemia in newborn rats is related to the severity of brain damage.

Previous studies have shown contradictory results regarding magnesium-mediated neuroprotection in animal models of perinatal asphyxia. The aim of this study is to investigate the effects of MgSO(4) postasphyxial treatment on hypoxia-ischemia (HI)-induced brain injury in neonatal rats and the possibility that this effect is related to the severity of brain damage. Seven-day-old rats underwent unilateral carotid artery ligation followed by 1 or 2 hours of hypoxia (8% O(2)) and MgSO(4) administration. Adenosine triphosphate/phosphocreatine and glutamate/glutamine measurements and neuropathological evaluation of the hippocampus were used to assess the effects of HI and MgSO(4). HI caused time-dependent changes in energy stores, amino acid concentrations, and brain damage. Administration of MgSO(4) after 1 hour but not after 2 hours of hypoxia resulted in significant prevention of HI-induced brain injury. MgSO(4) administration results in a significant protection against moderate HI-induced brain damage, whereas it fails to offer a similar effect against severe brain damage.