Nerve injury increases the susceptibility of motoneurons to N-methyl-D-aspartate-induced neurotoxicity in the developing rat

Abstract

If the sciatic nerve is crushed in neonatal rats, a large proportion of motoneurons die, but the same injury inflicted at five days of age results 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 motoneurons 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 reinnervate 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-aspartate, even after nerve injury. These results indicate that glutamate, the main excitatory neurotransmitter in the developing spinal cord, may be involved in the motoneuron death that occurs following nerve injury during early postnatal development.