PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term

Study design: Experimental study. Objectives: To investigate the effect of pre-treatment with PMX53, a C5aR antagonist, on spinal cord ischemia-reperfusion injury (IRI) in rat. Setting: 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). Conclusion: 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.