NERVE INJURY INCREASES THE SUSCEPTIBILITY OF MOTONEURONS TO N-METHYL-D-ASPARTATE-INDUCED NEUROTOXICITY IN THE DEVELOPING RAT

If the sciatic nerve is crushed in neonatal rats, a large proportion o f motoneurons die, but the same injury inflicted at five days of age r esults in little, if any, motoneuron death. However, these motoneurons are rendered susceptible to the excitotoxic effects of the glutamate agonist, N-methyl-D-aspartate. Retrograde labelling of soleus motoneur ons after nerve crush at five days of age, followed by treatment with N-methyl-D-aspartate seven days later, shows that only 36 +/- 7.5% of motoneurons have survived. If the motoneurons are allowed to reinnerva te their target, and N-methyl D-aspartate is applied three weeks after the nerve injury, no motoneuron death is observed. Furthermore, adult motoneurons remain resistant to the toxic effects of N-methyl-D-aspar tate, even after nerve injury. These results indicate that glutamate, the main excitatory neurotransmitter in the developing spinal cord, ma y be involved in the motoneuron death that occurs following nerve inju ry during early postnatal development.