Retrograde transfection of adenovirus vector carrying neurotrophin-3 gene enhances survival of anterior horn neurons of twy/twy mice with chronic mechanical compression of the spinal cord

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Chronic mechanical compression of the spinal cord causes neural tissue damage, including loss of anterior horn cells around the level of injury. Exogenous delivery of neurotrophins to neuronal cells could provide neuroprotection to spinal cord subjected to mechanical injury. We investigated the neuroprotective effects of targeted transfection of adenovirus vector (AdV) carrying neurotrophin (NT)-3 gene into twy (twy/twy) mouse spinal cord anterior horn neurons with chronic and progressive mechanical compression at C1-C2 level. AdV-NT-3 and AdV-p-galactosidase cDNA (LacZ) as a marker gene, were used for retrograde delivery via the sternomastoid muscle to the cervical spinal accessory motoneurons in 16-week-old adult twy mice with spinal cord compression. Four weeks after the AdV-NT-3 or AdV-LacZ injection, the compressed cervical spinal cord was examined histologically, immunohistologically and by immunoblot analysis. Immunoreactivity to NT-3 was significantly enhanced in AdV-NT-3-transfected twy mice than in AdV-LacZ injected mice. The numbers of anterior horn neurons of Nissl-, choline acetyltransferase-stained and wheat germ agglutinin-horseradish peroxidase-labeled neurons at the spinal cord level with maximum compression were significantly higher in AdV-NT-3-transfected than in AdV-LacZ-transfected twy mice. Retrograde AdV-NT-3 axonal transfection in twy mouse anterior horn neurons increased neurite axonal length and of arborization of WGA-HRP-labeled neurons. Our results suggest that targeted retrograde NT-3 gene delivery is feasible in the intact animal and that it enhances neuronal survival even under chronic mechanical compression of the spinal cord.