Targeted Retrograde Gene Delivery into the Injured Spinal Cord Using Recombinant Adenovirus Vector Carrying Neurotrophic Factor Gene

We investigated the efficacy of retrograde gene delivery via the sternomastoid muscle of recombinant adenovirus vector (AdV) carrying brain-derived neurotrophic factor (BDNF) gene for the rescue of injured rat spinal cord. AdV-BDNF gene or AdV-β-galactosidase (AdV-LacZ) gene was injected into the sternomastoid muscle immediately after traumatic C4 spinal cord injury. Localization of β-galactosidase expression produced by LacZ gene or AdV-BDNF gene transfection was examined by immunofluorescence staining and double staining of cell markers (NeuN, RIP, GFAP, OX-42, and NG2) in the injured spinal cord. TUNEL-positive cells were counted, and immunoreactivity to active caspase-3 and NG2 was examined after gene injection. Retrograde delivery of LacZ marker gene was identified in cervical spinal cord neurons and glial cells including oligodendrocytes in the white matter. AdV-BDNF transfection resulted in a significant decrease in the number of TUNEL-positive apoptotic cells by downregulating the caspase apoptotic pathway, with significant promotion of NG2 expression in injured spinal cord, compared with AdV-LacZ injection. Our results suggest that targeted retrograde BDNF gene delivery suppresses apoptosis of neurons and oligodendrocytes in the injured rat spinal cord.