Delayed application of IGF-I and GDNF can rescue already injured postnatal motor neurons.
IGF-I, GDNF, and other neurotrophic factors, when applied at the time of injury, can protect postnatal motor neurons from slow glutamate injury in organotypic 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 whether combinations of factors can further lengthen the therapeutic time window. Our data show that during a 7--8 week process of slow neurodegeneration either IGF-I or GDNF treatment, though delayed up to 4 weeks, still allowed substantial rescue of already injured motor neurons. However, the combination of both factors additively provided better neuroprotection than either factor alone, even after a 4-week delay. This proof of principle is relevant to the potential of IGF-I and GDNF as therapy for acquired disorders affecting motor neurons.
Bilak
M M
MM
Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287-7519, USA.
Kuncl
R W
RW
D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018698:Glutamic Acid / Q000633:toxicity; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D016900:Neurofilament Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology*; D013997:Time Factors
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I