Abstract
We have used adult rat peripheral nerve avulsion models to evaluate the effects of neuroprotective molecules on motoneuron degeneration. The right facial nerves of adult Fischer 344 male rats were avulsed and adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), transforming growth factor-beta2 (TGFbeta2), and growth inhibitory factor (GIF) were injected into the facial canal. The treatment with the vectors significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase (ChAT) immunoreactivity and suppressed the induction of nitric oxide synthase activity in these neurons. In separate experiments, animals were orally administered a solution of a neuroprotective compound T-588 after avulsion. Both free oral administration and oral tube administration of T-588 improved the survival of injured motoneurons and ameliorated their ChAT immunoreactivity. These results indicate that the gene transfer of GDNF, BDNF, TGFbeta2, and GIF and oral administration of T-588 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Animals
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Brain-Derived Neurotrophic Factor / administration & dosage
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Brain-Derived Neurotrophic Factor / genetics
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Diethylamines / administration & dosage
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Disease Models, Animal*
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Facial Nerve Injuries / therapy
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Gene Transfer Techniques
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Genetic Vectors
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Glial Cell Line-Derived Neurotrophic Factor / administration & dosage
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Glial Cell Line-Derived Neurotrophic Factor / genetics
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Male
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Metallothionein 3
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Motor Neuron Disease / genetics
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Motor Neuron Disease / pathology
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Motor Neuron Disease / therapy*
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Motor Neurons / pathology
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Nerve Degeneration / pathology
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Nerve Degeneration / prevention & control*
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Nerve Tissue Proteins / administration & dosage
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Nerve Tissue Proteins / genetics
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Neuroprotective Agents / administration & dosage*
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Peripheral Nerve Injuries*
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Peripheral Nerves / pathology
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Rats
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Thiophenes / administration & dosage
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Transforming Growth Factor beta / administration & dosage
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Transforming Growth Factor beta / genetics
Substances
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Brain-Derived Neurotrophic Factor
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Diethylamines
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Glial Cell Line-Derived Neurotrophic Factor
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Metallothionein 3
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Nerve Tissue Proteins
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Neuroprotective Agents
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Thiophenes
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Transforming Growth Factor beta
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T 588