title: Targeted retrograde gene delivery of brain-derived neurotrophic factor suppresses apoptosis of neurons and oligodendroglia after spinal cord injury in rats.
abstract: METHODS
  Histologic and immunohistochemical studies after targeted retrograde adenovirus (AdV)-mediated brain-derived neurotrophic factor (BDNF) gene delivery via intramuscular injection in rats with injured spinal cord.
  
  
  OBJECTIVE
  To investigate the neuroprotective effect of targeted retrograde AdV-BDNF gene transfection in the traumatically injured spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes.
  
  
  BACKGROUND
  Several studies investigated the neuroprotective effects of neurotrophins including BDNF on spinal cord injury, with respect to prevention of neural cell apoptosis in injured spinal cord. However, no report has described the potential effect of targeted retrograde neurotrophic factor gene delivery in injured spinal cord on prevention of neural cell apoptosis.
  
  
  METHODS
  AdV-BDNF or AdV-LacZ was used for retrograde delivery via bilateral sternomastoid muscles to the spinal accessory motoneurons immediately after spinal cord injury in rats. Localization of beta-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.
  
  
  CONCLUSIONS
  Our results suggest that targeted retrograde BDNF gene delivery suppresses apoptosis of neurons and oligodendrocytes in the injured rat spinal cord.
authors.affiliation: Department of Orthopaedics and Rehabilitation Medicine, The University of Fukui, Fukui, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Kenzo
authors.initials: K
authors.lastname: Uchida
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yayama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Alexander Rodriguez
authors.initials: AR
authors.lastname: Guerrero
authors.forename: Shoei
authors.initials: S
authors.lastname: Furukawa
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Baba
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002574:Cervical Vertebrae; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D018709:Statistics, Nonparametric
chemical_list: D019208:Brain-Derived Neurotrophic Factor