Increased mortality in female rats after severe diffuse traumatic brain injury is significantly attenuated by magnesium administration

Previous studies using focal models of traumatic brain injury have shown that female animals have a higher postinjury mortality than male animals, and that this higher mortality may be due to a worsened magnesium homeostasis in the female animals. The present study examined whether a similar difference in male and female mortality existed following a more diffuse model of traumatic brain injury and whether any mortality could be attenuated by ovariectomy or posttraumatic magnesium administration. Severe impact-acceleration induced diffuse brain trauma resulted in a 20% mortality in male rats as opposed to a 100% mortality in female animals (p< 0.05). This difference was not apparent at less severe injury levels. Administration of 750 mu moles/kg magnesium sulphate intramuscularly at 30 min after severe trauma reduced female mortality to 29% (p< 0.05). Female outcomes were similar in ovariectomised animals suggesting that the protective effects of magnesium were unrelated to cyclic changes in gonadal hormones. We conclude that the higher mortality observed in female animals following brain trauma is dependent on injury severity and that this mortality can be significantly attenuated with posttraumatic administration of magnesium sulphate.