Elsevier

Developmental Brain Research

Volume 81, Issue 2, 16 September 1994, Pages 162-170
Developmental Brain Research

Blockade of N-methyl-d-aspartate receptors by MK-801 (dizocilpine maleate) rescues motoneurones in developing rats

https://doi.org/10.1016/0165-3806(94)90302-6Get rights and content

Abstract

In rats following nerve injury at birth a large proportion of motoneurones to the soleus muscle dies. Blocking of N-methyl-d-aspartate (NMDA) receptors by MK-801 (dizocilpine maleate) for 12 days after nerve injury at birth leads to rescue of a proportion of motoneurones destined to die. Retrograde labelling of soleus motoneurones shows that 6–8 weeks after crushing the sciatic nerve in one hindlimb, only 10.9 ± 2.3% of the motonneurones have survived. In animals treated with an NMDA receptor blocker MK-801 (2 mg/kg i.p., from birth to 12 days old) 50.6± 3.8% of soleus motoneurones survived. This neuroprotective effect of MK-801 was dose dependant, since after treatment with lower doses (0.5 mg/kg; 1 mg/kg) fewer motoneurones survived (13.7% and 34.5%, respectively). To assess the effect of treatment with MK-801 on survival of α-motoneurones only, the number of soleus motor units was established physiologically. After nerve injury alone only 4.2± 1.2 of the 29–30 soleus motor units were present, while in animals treated with MK-801 (2 mg/kg) 14± 1.5 motor units were identified. The neuroprotective effect of MK-801 was not confined to soleus motoneurones but was also apparent on motoneurones to the extensor digitorum longus (EDL). In untreated EDL muscles of the 40 motor units only 5.5 ± 1.7 motor units survived neonatal nerve injury and this number increased to 18 ± 2.6 after treatment with MK-801. The neuroprotective effect of MK-801 was apparent regardless of whether the nerve lesion was carried out close to or far from the soleus muscle.

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