Rescue of rat anterior horn neurons after spinal cord injury by retrograde transfection of adenovirus vector carrying brain-derived 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. One hundred-thirty five adult Sprague-Dawley rats were used in the study with a standard weight-compression technique to produce spinal cord injury. AdV-BDNF gene or AdV-beta-galactosidase (AdV-LacZ) gene was injected into the sternomastoid muscle immediately after traumatic C4 segment spinal cord injury. AdV-BDNF was successfully appeared in the injured cervical spinal cord following injection into the sternomastoid muscle. BDNF expression in the anterior horn neurons of the cervical spinal cord reached peak levels at 1-2 weeks; and the expression persisted at significant levels for approximately 4 weeks after injury. AdV-BDNF transfection was associated with increased numbers of intact neurons as confirmed by Nissl, cholineacetyltransferase (ChAT), and acetylcholine esterase (AChE) staining especially from 2 weeks after injury, compared with the AdV-LacZ injected rats. Our results suggest that in vivo targeted retrograde AdV-BDNF-gene delivery may enhance neuronal survival following traumatic injury of the spinal cord.
Nakajima
Hideaki
H
Division of Orthopaedics and Rehabilitation Medicine, Department of Surgery, University of Fukui Faculty of Medical Sciences, Fukui, Japan. nhideaki@fmsrsa.fukui-med.ac.jp
Uchida
Kenzo
K
Kobayashi
Shigeru
S
Inukai
Tomoo
T
Horiuchi
Yukiko
Y
Yayama
Takafumi
T
Sato
Ryuichiro
R
Baba
Hisatoshi
H
D000110:Acetylcholinesterase / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000870:Anterior Horn Cells / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002470:Cell Survival / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D015316:Genetic Therapy; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007763:Lac Operon / Q000235:genetics; D008297:Male; D016472:Motor Neuron Disease / Q000209:etiology / Q000628:therapy*; D009046:Motor Neurons / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications / Q000628:therapy*; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D001616:beta-Galactosidase