Fe3O4 methylprednisolone plus calpain inhibitor protects against spinal cord ischemia-reperfusion injury in rats

Abstract

To investigate the neuroprotective effects of pretreatment with Fe3O4 methylprednisolone plus calpain inhibitor against spinal cord ischemia-reperfusion injury (SCI) in rats. A total of 18 male Sprague Dawley rats were randomly divided into sham operation, model, and pretreatment + SCI groups (receiving 25 mg/kg Fe3O4 methylprednisolone plus calpain inhibitor) (n = 6 each). The SCI model was established by clamping the left renal inferior abdominal aorta. Hindlimb motor function was evaluated 6, 12, 24, and 48 hours after reperfusion. At 48 hours after reperfusion, spinal cord tissues were collected for histopathological examination, measurement of oxidation product accumulation (malondialdehyde, MDA), and antioxidant enzyme activity assays [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX)]. Motor function scores were compared using non-parametric rank sum (Kruskal-Wallis) test, and mean tissue MDA content and antioxidant enzyme activities were compared using one-way analysis of variance. Compared with the sham operation group, the model group showed significantly increased MDA content (2.95 vs. 5.90 g mg; P = 0.023); significantly increased GSH-Px activity (0.31 vs. 0.78 U/mg; P = 0.001); significantly decreased SOD (16.03 vs. 8.37 U/mg; P = 0.001) and CAT (1.24 vs. 0.54 U/mg; P = 0.002) activities; and significantly decreased hindlimb motor function score at 6 hours (21 to 15.5; P =0.001). Compared with the model group, the pretreatment + SCI group showed significantly decreased MDA content (5.90 vs. 3.27 mg; P = 0.0355); significantly decreased GSH-Px activity (0.78 vs. 0.36 U/mg; P = 0.001); and significantly increased SOD (8.37 vs. 14.79 U/mg; P = 0.001) and CAT (0.54 vs. 0.89 U/mg; P = 0.043) activities. Histopathological changes were significantly less severe in the pretreatment + SCI group than in the model and sham operation groups (P < 0.05). Pretreatment with Fe3O4 methylprednisolone plus calpain inhibitor can prevent SCI by improving the balance between oxidation and antioxidant systems.