Pretreatment with erythropoietin attenuates the neurological injury after spinal cord ischemia

Abstract

Study design: Experimental study. Objectives: To investigate the effect of erythropoietin (EPO) pretreatment on spinal cord ischemic injury. Setting: Experimental Research Center at Seoul National University Bundang Hospital, Korea. Methods: Rats were treated with either 1000 IU kg À1 of EPO (EPO group, n¼8) or saline (control group, n¼8) 24 h before ischemia. Spinal cord ischemia was induced using a balloon-tipped catheter placed on the proximal descending aorta in the control group and the EPO group, but not in the sham group (n¼8). Neurological function was assessed using the motor deficit index (MDI; 0¼normal, 6¼complete paralysis) until 7 days after reperfusion, and histological examination of spinal cord was performed. Results: At the first day after reperfusion, the EPO group demonstrated a significantly lower MDI compared with the control group (2.0 (0.3-2.0) vs 4.0 (3.0-4.8), median (interquartile range); EPO group vs control group, respectively; P¼0.002). This trend was sustained until 7 days after reperfusion (1.0 (1.0-1.8) vs 4.5 (3.3-5.0); EPO group vs control group, respectively; P¼0.001), and more normal motor neurons (29.9±3.1 vs 21.4±3.4, mean±s.d.; EPO group vs control group, respectively; Po0.001) were observed. However, compared with the sham group, the EPO group displayed a significantly higher MDI (0.0, sham group) and fewer intact motor neurons (37.8 ± 5.5, sham group; Po0.001, sham vs control group). Conclusion: Pretreatment with EPO significantly attenuates neurological injury following spinal cord ischemia, although it cannot completely abolish the ischemic injury.

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

“…EPO was first reported to dramatically improve functional neurological status in a rabbit ischemia SCI model . This kind of functional recovery was also demonstrated in rat, mouse, pig, and other rabbit models.…”

Effects of erythropoietin and methylprednisolone on AQP4 expression in astrocytes

“…The protective effects of EPO in astrocytes may be mediated through the activation of c-Jun N-terminal kinase, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathways ( 35 , 36 ). EPO treatment has been demonstrated to preserve the neurological function and to attenuate neuronal cell damage in a mouse model of spinal cord IR injury ( 37 ), and it has been reported to significantly suppress edema formation and prevent neurological injury following spinal cord ischemia in rats ( 38 ). Furthermore, EPO administration has been reported to protect the integrity of the BBB, and its beneficial effects during BBB disruption have been associated with increased levels of AQP4 ( 39 – 41 ).…”

A peroxisome proliferator-activated receptor gamma agonist attenuates neurological deficits following spinal cord ischemia in rats

“…Spinal cord ischemia was induced by placement of a balloon-tipped catheter in the thoracic aorta as described previously. 2 In brief, after surgical incision, a balloon-tipped catheter (Fogarty Arterial Embolectomy Catheter; Edward Life Sciences, Irvine, Calif) was inserted into the femoral artery and advanced into the descending thoracic aorta. The right carotid artery was exposed and cannulated with a 20-gauge intravenous catheter, which was connected to an external blood reservoir.…”