Protection of motoneurons by prior muscle damage

We previously reported (Soc. Neurosci. Abs., 26: 792), that intramuscular injection of a splice variant of the gene for IGF-1 (MGF) largely prevented the loss of adult rat facial motoneurons after nerve avulsion. Since muscle stretch and damage are potent stimuli for MGF expression, we examined the degree of neuroprotection conferred by these perturbations of muscle alone. The right snout of adult Sprague-Dawley rats (n=6/group) was injected with physiological saline ('mechanical injury'), 0.5% w/v bupivacaine in saline ('mechanical and toxic injury') or distilled water ('mechanical and osmotic injury'). After 7 days the right facial nerve was avulsed. After a further 28 days, total numbers of facial motoneurons were estimated using an optical disector method (Brain Res. Prot. 2001, 8: 113-125). In all experimental groups, there was a significant (p=0.05, Mann-Whitney U-test) loss of motoneurons ipsilaterally compared to both the contralateral side and normal controls. This amounted to 75% loss in the avulsion-only group, but only 55%, 49% and 32% loss for the saline, bupivacaine and distilled water-treated animals, respectively. When compared to the avulsion-only group, the neuroprotection afforded by muscle stretch/damage was statistically significant (p=0.05). Histological examination of the snout muscle 4d after injection showed a correlation between the degree of tissue lymphocytic infiltration and the degree of neuroprotection provided. Our results indicate that prior damage to the target tissue of motoneurons renders them more resistant to axotomy-induced death.