Effects of brain-derived neurotrophic factor (BDNF) on compression-induced spinal cord injury: BDNF attenuates down-regulation of superoxide dismutase expression and promotes up-regulation of myelin basic protein expression.
Neurotrophins enhance the survival of cells in the nervous system under both physiological and pathological conditions, such as those caused by disease or trauma. We recently demonstrated that expression of brain-derived neurotrophic factor (BDNF) was up-regulated in neurons and glia after compression-induced spinal cord injury (SCI). We show here the effects of BDNF on the oligodendrocyte survival and functional recovery after SCI. The effects of intrathecally administered BDNF on both Cu/Zn superoxide dismutase (CuZnSOD) and myelin basic protein (MBP) expression were examined using rats that had received compression-induced spinal cord injury. CuZnSOD expression in the spinal cord was down-regulated within 24 h of compression-induced injury and then recovered. Continuous infusion of BDNF inhibited the acute down-regulation of CuZnSOD expression. In situ hybridization showed that CuZnSOD was expressed in both neurons and glia. Although MBP expression was greatly reduced after injury, BDNF administration promoted the recovery of MBP expression nearly to a control level after 2 wk. Furthermore, BDNF administration also prompted behavioral recovery. These results suggest BDNF's usefulness in human clinical applications. The attenuation of CuZnSOD down-regulation may be related to a protective effect of BDNF and the promotion of MBP up-regulation may be related to a long-lasting restorative effect.
Ikeda
Osamu
O
Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Japan.
Murakami
Masazumi
M
Ino
Hidetoshi
H
Yamazaki
Masashi
M
Koda
Masao
M
Nakayama
Chikao
C
Moriya
Hideshige
H
D000818:Animals; D015152:Blotting, Northern; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009043:Motor Activity; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D016166:Free Radical Scavengers; D004676:Myelin Basic Protein; D013482:Superoxide Dismutase