The tissue-protective effect of magnesium sulfate against damage in the fetal rat brain and placenta in intrauterine ischemia-reperfusion injury

Perinatal hypoxic-ischemic brain injury is a major cause of neonatal mortality, morbidity, and long-term neurological deficits, including cerebral palsy, mental retardation, and epilepsy. This study aims to assess the tissue-protective effects of N-methyl-D-aspartate antagonist magnesium sulfate, when administered before and during ischemic injury in a prenatal hypoxia-reperfusion rat model, focusing on the fetal brain and placenta. Twenty-four pregnant rats at 19 days of gestation (term, 21 days) were assigned to four groups (n=6 each): (1) Negative controls, (2) Positive controls (ischemia-reperfusion injury), (3) Prophylactic magnesium sulfate (administered 30 minutes before ischemic injury), and (4) Concurrent magnesium sulfate (administered simultaneously with ischemic injury). The ischemia-reperfusion model involved laparotomy, 20-minute utero-ovarian artery ligation, and 30-minute reperfusion. Prophylactic treatment consisted of intraperitoneal administration of 600 mg/kg magnesium sulfate 30 minutes pre-ischemia. Fetal brain and placental tissues were collected post-reperfusion. Histopathological changes (hyperemia, hemorrhage, infiltration) were scored, and immunohistochemical analyses of tumor necrosis factor-alpha and caspase-3 expression were conducted. Magnesium sulfate significantly reduced histopathological damage (p<0.001) and alleviated tumor necrosis factor-alpha and caspase-3 expressions (p<0.001). Prophylactic administration demonstrated greater tissue-protective effects than concurrent treatment. These findings suggest that magnesium sulfate may offer neuroprotection against perinatal hypoxia-reperfusion injury, with potential clinical implications. Keywords: fetal hypoxia, hypoxia-reperfusion injury, magnesium sulfate