Influence of FK506, cyclosporin A, testosterone and nimodipine on motoneuron survival following axotomy

Injury to immature motoneurons results in extensive nerve cell death. Avuls ion injury in adult animals has a similar effect. Rescuing injured neurons from degeneration and death is a prerequisite for successful functional rec overy. Here, we have explored the possible survival promoting effect of the immunosuppressant agents FK506 and cyclosporin A, the calcium channel bloc ker nimodipine as well as testosterone on axotomized neonatal facial motone urons. In addition, we examined the effect of cyclosporin A and Nimodipine, a calcium channel blocker, on survival of adult motoneurons following hypo glossal nerve avulsion. FK506 and cyclosporin A were administered intraperi toneally, testosterone intramuscularly and Nimodipine via the food. After t he appropriate postoperative survival periods, the number of surviving faci al or hypoglossal motoneurons respectively was calculated. FK506 and Cyclos porin A were found to enhance facial motoneuron survival following neonatal axotomy. Cyclosporin A and Nimodipine were found to promote motoneuron sur vival in adult rats after hypoglossal nerve avulsion. Nimodipine possibly a lso reduced motoneuron death in neonatal rats twenty-one days after facial nerve transection, but failed to rescue motoneurons in neonatal rats during the first seven days after nerve injury. Treatment with testosterone was i neffective in preventing neonatal facial motoneurons from axotomy-induced d eath at seven days postaxotomy. The results indicate that motoneuron degene ration can be counteracted to a large extent by immunosuppressant agents as well as by calcium channel blockers. Taken together with findings from pre vious studies, we conclude that motoneuron survival following axotomy can b e promoted by a variety of endogenous and exogenous molecules acting on dif ferent cellular mechanisms.