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 effects of N-methyL-D-aspartate. Treatment with dizocilpine maleate, an antagonist of this receptor, has been shown to rescue a proportion of those motoneurons destined to die following nerve injury at birth. However, this is a relatively toxic compound. In this study we examined whether systemic treatment with magnesium sulphate, a non-competitive antagonist 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 nerve injury at five days followed by exposure to N-methyl-D-aspartate. The number of surviving motoneurons reinnervating the tibialis anterior and extensor digitorum longus muscles were counted using retrograde labelling. Following nerve injury at birth and treatment with magnesium sulphate, there was a small increase in the survival of injured motoneurons, although this improvement was not significant. Nerve injury at five days does not result in motoneuron death, but when followed by treatment 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 motoneuron survival, so that 67 +/- 5.8% of motoneurons survived. Thus, systemic treatment with magnesium can prevent the death of motoneurons rendered susceptible to the excitotoxic effects of N-methyl-D-aspartate by nerve injury. These results also indicate that an increased susceptibility 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.