title: Vector-mediated expression of erythropoietin improves functional outcome after cervical spinal cord contusion injury.
abstract: We evaluated the therapeutic effect of erythropoietin (EPO) delivered by direct injection of a nonreplicating herpes simplex virus (HSV)-based vector coding for EPO (vEPO) in a model of cervical hemicord contusion at C7. At 1 h after spinal cord injury (SCI), either vEPO or control vector carrying a reporter gene (vC) was injected into the cord above and below the lesion. Animals injected with vEPO showed a statistically significant improvement in the ipsilateral forelimb function, as measured by open-field evaluation of motor performance, forelimb reaching in the cylinder test and misplacement in grid walk. This correlated with preservation of gray matter in the area of the lesion. There was also mild but significant improvement of hindlimb motor function measured by Basso-Beattie-Bresnahan score and computerized gait analysis in vEPO compared with control vector-injected animals. Microtubule-associated protein tau, phosphorylated and nonphosphorylated neurofilament protein and the synaptic proteins synaptophysin and PSD-95 were all significantly increased in the spinal cord of vEPO-treated animals compared with control vector-injected animals. These data suggest that gene transfer of EPO after cervical SCI by minimizing the injury size and enhancing tissue sparing preserves large-caliber axons and promotes synaptogenesis.
authors: Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, Ann Arbor, MI 48109, USA.
authors: S
authors: S
authors: Wang
authors: Z
authors: Z
authors: Wu
authors: P
authors: P
authors: Chiang
authors: D J
authors: DJ
authors: Fink
authors: M
authors: M
authors: Mata
mesh_terms: D000818:Animals; D003288:Contusions / Q000628:therapy*; D004921:Erythropoietin / Q000235:genetics*; D005260:Female; D005552:Forelimb / Q000503:physiopathology; D005822:Genetic Vectors; D006614:Hindlimb / Q000503:physiopathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D018139:Simplexvirus / Q000235:genetics*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D014162:Transfection
chemical_list: D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D004921:Erythropoietin