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Effect of Long-Term, Postasphyxial Administration of Magnesium Sulfate on Immunostaining of Microtubule-Associated Protein-2 and Activated Caspase-3 in 7-Day-Old Rat Brain

Perinatal Center and Department of Obstetrics and Gynecology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan hsameshima{at}fc.miyazaki-med.ac.jp

Tsuyomu Ikenoue, MD, PhD

Perinatal Center and Department of Obstetrics and Gynecology, Miyazaki Medical College, Miyazaki, Japan

Objective: To test whether magnesium inhibits apoptosis during hypoxia-iscema (HI) in the developing brain, we studied the effect of long-term magnesium treatment on an early marker of neuronal damage (loss of microtubule-associated protein-2; MAP-2) and a marker of apoptosis (activated caspase-3) after HI in newborn rats.

Methods: Seven-day-old rat pups (n = 107) were exposed to unilateral carotid artery ligation and 2 hours of hypoxia (8% oxygen in 92% nitrogen). Magnesium was administered by a micro-osmotic pump implanted iin the back, at an infusion rate of 75 mg/kg per hour for 3 days. Neuronal loss in the cerebral cortex and hippocampus was evaluated by loss of MAP-2 at 24 and 48 hours after HI and visually ranked by a semiquantitative, three-point scale (mild, moderate, and severe). Caspase-3 activation was evaluated similarly in an adjacent section. Area and severity of the damaged lesion were compared between the two staining methods and between magnesium and controls, by ² test and Fisher test.

Results: Three-day magnesium administration reduced loss of MAP-2 (from 33 of 50 to 21 of 45, P = .06) and activation of caspase-3 (from 34 of 50 to 21 of 45, P = .04) in the cerebral cortex after HI. There was no significant change in these immunostainings in the hippocampal regions. In the hippocampal CA3, the severity ranked by activated caspase-3 staining was significantly less than that of MAP-2 staining.

Conclusion: Long-term, post-HI treatment with magnesium inhibited caspase-3 activation and MAP-2 immunostaining, suggesting that magnesium inhibited apoptotic neuronal death of HI in 7-day-old rats.

Key Words: Hypoxia-ischemia • newborn rat brain • magnesium • activated caspase-3 • microtubule-associated protein -2

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