PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term.
METHODS
Experimental study.


OBJECTIVE
To investigate the effect of pre-treatment with PMX53, a C5aR antagonist, on spinal cord ischemia-reperfusion injury (IRI) in rat.


METHODS
Department of Neurosurgery, Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi Province, China.


METHODS
IRI was induced in the lumbar spinal cord by applying a mini aneurysm clamp to the abdominal aorta for 60 min in adult Sprague-Dawley rats. PMX53 (1 mg kg(-1)) was administered through femoral vein injection 30 min before ischemia on the rats in the PMX53 group (n=18). The saline group (n=18) was given saline at the same volume through femoral vein injection. The neurologic outcome of the posterior limbs was assessed by the Basso-Beattie-Bresnahan (BBB) score at 1, 6, 12, 24 and 48 h after reperfusion. Histologic changes of the spinal cord were detected with hematoxylin-eosin (H-E) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect myeloperoxidase (MPO) activity in the spinal cord. Immunohistochemistry was used to investigate the quantity of activated astrocytes and microglia.


RESULTS
After pre-treatment with PMX53, neurologic function improved gradually after 6, 12, 24 and 48 h reperfusion. The BBB score of the PMX53 group increased significantly (P<0.05) compared with the saline group. H-E staining showed that pathologic damage in the PMX53 group was reduced. Moreover, administration of PMX53 significantly inhibited neutrophil infiltration in the spinal cord. Levels of MPO activity in the spinal cord were remarkably lower in the PMX53 group (P<0.05). There were also more activated microglia and astrocytes in the spinal cord of the PMX53 group than in the saline group (P<0.05).


CONCLUSIONS
PMX53 delivered 30 min prior to ischemic injury protects the spinal cord from IRI, probably via the inhibition of neutrophil activity, increased activated microglia and astrocyte.
Department of Neurosurgery, Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, China.
Q
Q
Dong
Department of Ultrasound, Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, China.
L
L
Sun
Department of Emergency Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, China.
L
L
Peng
Department of Emergency Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, China.
B
B
Yan
Department of Neurosurgery, Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, China.
J
J
Lv
Department of Emergency Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, China.
G
G
Wang
Department of Neurosurgery, Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, China.
S
S
Gong
D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004334:Drug Administration Schedule; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007155:Immunologic Factors / Q000627:therapeutic use*; D008840:Microfilament Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D009460:Neurologic Examination; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
C438957:AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg); C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D007155:Immunologic Factors; D008840:Microfilament Proteins; D010456:Peptides, Cyclic; D009195:Peroxidase