Protective effect of C1 esterase inhibitor on acute traumatic spinal cord injury in the rat.
OBJECTIVE
The complement system and activated neutrophils are thought to play a major role in initiating some of the inflammatory events that occur in spinal cord injury. The aim of the present study was to assess the effects of C1 esterase inhibitor (C1-INH) on traumatic spinal cord injury (SCI) in the rat.


METHODS
Thirty-eight male Wistar rats were used. Just after SCI by a pneumatic impact device, C1-INH (n=16, C1-INH group) or saline (n=16, saline group) was administered. Sham operated animals (n=6, sham group) received only laminectomy. Eighteen (six from each group) rats were killed and an assessment of leukocyte infiltration by myeloperoxidase (MPO) activity and immunoreactivity of MPO were performed 24 hours after SCI. Twenty (ten from each of C1-INH and saline groups) rats were examined using behavioral function on post-operative days. They were also examined after 7 days by histologic analysis using Luxol fast blue for axons and myelin. Lesion volume was calculated by considering a lesion as being composed of two cones with juxtaposed bases. During the experiment, sequential changes in regional spinal cord blood flow (rSCBF) were measured using the laser Doppler (LD) scanning technique.


RESULTS
The recovery of motor function was better in the C1-INH group than in the saline group. In the C1-INH group, immunoreactivity of MPO showed a tendency to be smaller than that of the saline group. Lesion volume was significantly smaller in the C1-INH group than in the control group (p<0.01) and MPO activity was also significantly smaller in the C1-INH group than in the control group (p<0.01). After SCI, the rSCBF value decreased gradually and significantly in both injured groups. Significant differences were observed from 30 to 120 minutes after SCI (p<0.05).


CONCLUSIONS
The results of this study provided the first evidence that C1-INH reduced accumulation of polymorphonuclear leukocytes (PMLs) and neuronal damage in acute stage after SCI. This protection was not related to an improvement in rSCBF.
Tei
Rinsei
R
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Kaido
Takanobu
T
Nakase
Hiroyuki
H
Sakaki
Toshisuke
T
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D050718:Complement C1 Inhibitor Protein / Q000494:pharmacology* / Q000627:therapeutic use; D003173:Complement C1s / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010243:Paralysis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D009195:Peroxidase / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D016896:Treatment Outcome
D050718:Complement C1 Inhibitor Protein; D018696:Neuroprotective Agents; D003165:Complement System Proteins; D009195:Peroxidase; D003173:Complement C1s