Targeted retrograde gene delivery of neurotrophic factor suppresses apoptosis of neurons and oligodendrocytes after rats spinal cord injury
Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine
Faculty of Medical Sciences, University of Fukui
Eiheiji, Fukui 910-1193, Japan
Abstract:
Objectives:
To investigate the neuroprotective effect of targeted retrograde adenovirus-mediated brain-derived neurotrophic factor (AdV-BDNF) gene transfection in the traumatically injured spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes.
Methods:
AdV-BDNF or AdV-LacZ was used for retrograde delivery via sternomastoid muscles to the spinal accessory motoneurons immediately after spinal cord injury in rats. 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.
Results:
Retrograde delivery of LacZ marker gene was identified in cervical spinal 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.
Conclusion:
Our results suggest that targeted retrograde BDNF gene delivery suppresses apoptosis of neurons and oligodendrocytes in the injured rat spinal cord.
