Neurotrophin-4/5 postpones the death of injured spinal motoneurons in newborn rats.

We have compared the short- and long-term effects of Neurotrophin-4/5 (NT-4/5) on the survival of spinal motoneurons in neonatal rats. To this aim, the sciatic nerve was cut in newborn rats and NT-4/5 or buffer were applied to the proximal nerve stem in a gelfoam as well as by daily local injection. The number of motoneurons or ventral root fibers was determined 4, 11, and 14 days later. Four days after received NT-4/5 lost only 19% + 2.7% (540 + 81). No systemic effect on the contralateral motoneurons was observed. Surprisingly, 11 and 14 days following the operation, the loss of motoneurons and of ventral root fibers was the same in buffer and NT-4/5 treated animal despite the daily treatment. Thus, although NT-4/5 is a potent survival factor for motoneurons in culture and can transiently prevent the death of motoneurons in vivo, it can not, under these experimental conditions, permanently rescue lesioned motoneurons. These results indicate that other trophic factors or combinations of factors may be required to permanently prevent the death of spinal motoneurons and that the short term survival promoting effects of neurotropic factors in motoneuron lesion models can not be used to predict their therapeutic potential in chronic neurodegenerative disorders.