MAGNESIUM-IONS REDUCE MOTONEURON DEATH FOLLOWING NERVE INJURY OR EXPOSURE TO N-METHYL-D-ASPARTATE IN THE DEVELOPING RAT

Developing motoneurons can be induced to die by target deprivation and there is evidence that this cell death involves the excitotoxic effec ts of N-methyL-D-aspartate. Treatment with dizocilpine maleate, an ant agonist of this receptor, has been shown to rescue a proportion of tho se motoneurons destined to die following nerve injury at birth. Howeve r, this is a relatively toxic compound. In this study we examined whet her systemic treatment with magnesium sulphate, a non-competitive anta gonist of the N-methyl-D-aspartate receptor which is better tolerated than dizocilpine maleate, could prevent motoneuron death. Motoneurons were induced to die either by sciatic nerve injury at birth or by nerv e injury at five days followed by exposure to N-methyl-D-aspartate. Th e number of surviving motoneurons reinnervating the tibialis anterior and extensor digitorum longus muscles were counted using retrograde la belling. Following nerve injury at birth and treatment with magnesium sulphate, there was a small increase in the survival of injured motone urons, although this improvement was not significant. Nerve injury at five days does not result in motoneuron death, but when followed by tr eatment with N-methyl-D-aspartate, only 42 +/- 2.9% of motoneurons to these flexor muscles survived. Treatment with magnesium sulphate prior to injection of N-methyl-D-aspartate significantly increased motoneur on survival, so that 67 +/- 5.8% of motoneurons survived. Thus, system ic treatment with magnesium can prevent the death of motoneurons rende red susceptible to the excitotoxic effects of N-methyl-D-aspartate by nerve injury. These results also indicate that an increased susceptibi lity to the excitotoxic effects of glutamate is likely to play a role in the death of motoneurons denied contact with their target during a critical period of their development.