Combination of dexamethasone and aminoguanidine reduces secondary damage in compression spinal cord injury.
The study was performed to investigate the effect of combination therapy with aminoguanidine (AG) and dexamethasone (DEX) on the compression spinal cord injury (SCI) in rat. Compared to the control group, the combination therapy group with AG (75 mg/kg) and DEX (0.025 mg/kg) significantly reduced the degree of (1) spinal cord edema, (2) the permeability of blood spinal cord barrier (measured by (99m)Tc-Albumin), (3) infiltration of neutrophils (MPO evaluation), (4) cytokines expression (tumor necrosis factor-alpha and interleukin-1 beta), and (5) apoptosis (measured by Bax and Bcl-2 expression). In addition, we have also clearly demonstrated that the combination therapy significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly indicated for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of SCI.
Xu
Wei-Bing
WB
Department of Orthopaedics, Dalian Municipal Central Hospital, Da Lian, 116033, Liaoning Province, People's Republic of China. xwb2008999@yahoo.com.cn
Lv
Gang
G
Wang
Yan-Feng
YF
Lu
Xu-Hua
XH
Huang
Tao
T
Zhu
Yue
Y
Jia
Lian-Shun
LS
D000818:Animals; D015153:Blotting, Western; D001826:Body Fluids; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013117:Spinal Cord Compression / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D006146:Guanidines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone; D009195:Peroxidase; C004479:pimagedine