An adenovirus vector for neurotrophin transfection induces compressed spinal cord of adults rat

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We investigated neurotrotective effect of glial cell lined-derived neurotrophic factor (GDNF) encoded by an adenovirus vector (AxCAhGDNF) on the injured spinal cord lesions. The rat thoracic spinal cord was experimentally injured by extradural static weight compression. After the direct injection of the adenovirus vector into thoracic spinal cord, histological and immunohistochemical analysis and immunoblot analysis were examined. One week after the injury with AxCAlacZ, the animals showed expression of β-galactosidase activity in injured and injected lesions and the expression was visualized until 4-6 weeks after injection. Animals injured and injected with AxCAhGDNF showed intense immunolabeling for GDNF in lesioned spinal cord motoneurons, reactive astrocyte and oligodendrocyte, and expression of virus induced human GDNF mRNA transcripts in the spinal cord tissue. Nissl-stained cell counts revealed that the injection with AxCAhGDNF significantly prevented the loss of lesioned spinal cord motoneurons 2-4 weeks after injury. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with spinal cord injury.