Effect of combined treatment with methylprednisolone and Nogo-A monoclonal antibody after rat spinal cord injury.
The purpose of this study was to investigate the effects of combination therapy with methylprednisolone (MP) and Nogo-66 antagonistic peptide (NEP1-40) on morphological and functional recovery in adult rats subjected to thoracic compression spinal cord injury (SCI). Animals were randomized into four groups: a trauma control group, an MP group, an NEP1-40 group, and a combined treatment group. The inflammatory reaction, neuronal and oligodendrocyte survival, and ultrastructure were assessed at the injury site. Functional analysis was also performed using Basso, Beattie and Bresnahan (BBB) scoring. Rat behaviour was evaluated regularly up to week 4. NEP1-40 did not alter the beneficial effect of MP on haematogenous inflammatory cell infiltration, while combined treatment resulted in greater neuronal and oligodendrocyte survival compared with monotherapy or control. Combination therapy resulted in better locomotor scores. These results in a clinically-relevant SCI model showed that significant neuroprotection can be obtained by combining an initial acute IV injection of MP with continuously infused NEP1-40.
Wu
J
J
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Yang
H
H
Qiu
Z
Z
Zhang
Q
Q
Ding
T
T
Geng
D
D
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D058851:GPI-Linked Proteins; D008775:Methylprednisolone / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009185:Myelin Proteins / Q000276:immunology*; D000070816:Nogo Receptor 1; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; C509624:NEP1-40 protein, human; D000070816:Nogo Receptor 1; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C486581:Rtn4r protein, rat; D008775:Methylprednisolone