Protective effects of adenoviral cardiotrophin-1 gene transfer on rubrospinal neurons after spinal cord injury in adult rats.
Cardiotrophin-1 (CT-1), a muscle-derived cytokine, supports the survival of motoneurons in vivo and in vitro. The present study investigated whether adenoviral huCT-1 gene transfer protected injured neurons from cell death or atrophy and promoted regeneration of rubrospinal tract (RST) after spinal cord injury in adult rats. Administration of the adenoviral CT-1 vector (Adv-CT1) to C3-4 lateral funiculus hemisection cavity, that completely interrupted RST, led to sustained CT-1 expression. Providing Adv-CT1, which rescued 20% of neurons, could prevent the loss of injured rubrospinal neurons 8 weeks post-injury. Retrograde tracing with FluoroGold showed that 1.2% of RST neurons regenerated at least two segments caudal to the injury site. Anterograde tracing with biotinylated dextran amine revealed that the RST axons terminated in white matter and gray matter. Behavioral testing revealed a significant functional recovery in limb usage. This observation indicated that adenoviral CT-1 gene transfer into the injured cord promoted survival and regeneration of rubrospinal neurons in adult rats.
Zhang
Zhang-Feng
ZF
Department of Neurotrauma, Research Institute of Surgery, Third Military Medical University, Chongqing 400042, P.R. China. zhang__zzf@yahoo.com.cn
Liao
Wei-Hong
WH
Yang
Qing-Feng
QF
Li
Hong-Yun
HY
Wu
Ya-Min
YM
Zhou
Xin-Fu
XF
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001710:Biotin / Q000031:analogs & derivatives*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics*; D003911:Dextrans; D005260:Female; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D006579:Heterozygote; D007150:Immunohistochemistry; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012012:Red Nucleus / Q000166:cytology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology*; D013266:Stilbamidines; D019076:Transgenes / Q000235:genetics
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D016207:Cytokines; D003911:Dextrans; D005456:Fluorescent Dyes; D013266:Stilbamidines; C076397:biotinylated dextran amine; D001710:Biotin; C092073:cardiotrophin 1