Combined therapy of methylprednisolone and brain-derived neurotrophic factor promotes axonal regeneration and functional recovery after spinal cord injury in rats.
OBJECTIVE
To investigate the effects of combination therapy with methylprednisolone (MP) and brain-derived neurotrophic factor (BDNF) on axonal remyelination and functional recovery after spinal cord injury in rats.


METHODS
Forty-five rats were randomly divided into three groups: Group A received MP and BDNF; group B received MP and cerebrospinal fluid (CSF); and group C received CSF only. Contusion injury to adult rat spinal cord was produced at the T(10) vertebra level followed by immediate intravenous MP or CSF, and was thereafter infused intrathecally with BDNF or CSF for 6 weeks. Axonal remyelination and functional recovery was observed using RT-PCR, immunohistochemistry and open field locomotion.


RESULTS
An increase of 28.4% +/- 2.3% in the expression of proteolipid protein (PLP) gene, an endogenous indicator of axonal remyelination, was demonstrated in group A 24 hours after injury. Ten weeks later, there were significant decreases in hematogenous inflammatory cellular infiltration in groups A and B compared to C (P < 0.05). Concomitantly, a significant amount of axonal remyelination was observed in group A compared to groups B and C (P < 0.05). Furthermore, combination therapy using MP and BDNF in group A resulted in stimulation of hindlimb activity as well as improvement in the rate of functional recovery in open field locomotion (P < 0.05).


CONCLUSIONS
Combined therapy of MP and BDNF can improve functional recovery through mechanisms that include attenuating inflammatory cellular infiltration and enhancing axonal remyelination at the injury site. Such a combination may be an effective approach for treatment of spinal cord injury.
Li
Lixin
L
Department of Neurosurgery, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. lilixin2@hotmail.com
Xu
Qiwu
Q
Wu
Youzhang
Y
Hu
Weixing
W
Gu
Peiyuan
P
Fu
Zhen
Z
D000818:Animals; D001369:Axons / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D008775:Methylprednisolone / Q000008:administration & dosage*; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009416:Nerve Regeneration / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D008775:Methylprednisolone