Delayed application of IGF-1 and GDNF can rescue already injured postnatalmotor neurons

IGF-I, GDNF, and other neurotrophic factors, when applied at the time of in jury, can protect postnatal motor neurons from slow glutamate injury in org anotypic spinal cord. However, in human spinal cord diseases, motor neuron injury is already established when treatment could begin. We tested whether neurotrophic factors can protect already-injured motor neurons, and whethe r combinations of factors can further lengthen the therapeutic time window. Our data show that during a 7-8 week process of slow neurodegeneration eit her IGF-I or GDNF treatment, though delayed up to 4 weeks, still allowed su bstantial rescue of already injured motor neurons. However, the combination of both factors additively provided better neuroprotection than either fac tor alone, even after a 4-week delay. This proof of principle is relevant t o the potential of lGF-I and GDNF as therapy for acquired disorders affecti ng motor neurons. NeuroReport 12:2531-2535 (C) 2001 Lippincott Williams & W ilkins.