SCAVENGERS OF FREE OXYGEN RADICALS IN COMBINATION WITH MAGNESIUM AMELIORATE PERINATAL HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE RAT

The effect of oxygen radical scavengers in combination with magnesium administered after a hypoxic-ischemic insult was evaluated in a model of perinatal brain damage. A mixture of scavengers of oxygen-derived free radicals (L-methionine, 0.2 g; mannitol, 0.5 g) and magnesium sulfate (0.3 g) per kg body weight was given to 34 1-wk-old rat pups immediately after a session of unilateral carotid artery ligation and 2 h of hypoxia (8% O2 in N2). Thirty-four littermates served as controls; they received a placebo. At 3 wk of age, there was a significantly smaller reduction of hemisphere weight ipsilateral to the ligation in the treated animals compared with the controls (0.7 versus 8.8% of contralateral hemisphere weight median values, p < 0.01). The difference was especially marked for the most severe degrees of brain damage. Only one of the 34 treated animals, compared with 13 of 34 control animals, had a reduction of ipsilateral hemisphere weight >25%. The protection offered by the mixture used was larger than in previously published studies using this model and treatment after the hypoxic exposure with only one protective agent. It is concluded that a combination of oxygen radical scavengers and magnesium administered in the phase of resuscitation mitigates perinatal postasphyxial brain damage in the rat. An additive protective effect of different therapeutic strategies on the brain damage may be present in this situation.