Kohji Utada1, Kazuyoshi Ishida2, Suguru Tohyama3, Yutaka Urushima4, Yoichi Mizukami5, Atsuo Yamashita6, Masato Uchida7, Mishiya Matsumoto8. 1. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. utada@yamaguchi-u.ac.jp. 2. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. ishid002@yamaguchi-u.ac.jp. 3. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. sugurutohyama@yahoo.co.jp. 4. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. t003uf@yamaguchi-u.ac.jp. 5. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. mizukami@yamaguchi-u.ac.jp. 6. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. ymst2699@yamaguchi-u.ac.jp. 7. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. uch0809@yamaguchi-u.ac.jp. 8. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. mishiya@yamaguchi-u.ac.jp.
Abstract
INTRODUCTION: Insulin-like growth factor 1 (IGF-1) and erythropoietin (EPO) have been reported to independently protect against ischemic spinal cord injury in rabbits. In the present study, we investigated whether the combination of IGF-1 and EPO protects against ischemic spinal cord injury in rabbits. METHODS: Animals were assigned to 1 of 4 groups (n = 6 in each): a control group (saline), an IGF-1 group (IGF-1 0.3 mg/kg), an EPO group (EPO 800 U/kg), or an IGF-1 + EPO group (IGF-1 0.3 mg/kg + EPO 800 U/kg). Spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. Saline, IGF-1, and EPO were administered intravenously just after the start of reperfusion. Hindlimb motor function was assessed daily for 7 days, after which histopathological evaluation was performed. To analyze phosphorylation of signal transduction molecules, animals were assigned to 1 of the 4 groups (n = 8 in each). Spinal cord ischemia and the treatment were the same as those described above. The spinal cords were removed at 15 or 30 min after reperfusion and used to analyze phosphorylation of signal transduction molecules. Four animals served as the preischemic control, and the spinal cord was removed just before the start of ischemia. RESULTS: In the IGF-1 + EPO group, both neurological and histopathological outcomes were significantly improved as compared to the control group, which was consistent with the increase of Janus kinase-2 (JAK2) phosphorylation. CONCLUSIONS: The combination of IGF-1 and EPO protects against ischemic spinal cord injury in rabbits. JAK2 might contribute to the protective effect.
INTRODUCTION:Insulin-like growth factor 1 (IGF-1) and erythropoietin (EPO) have been reported to independently protect against ischemic spinal cord injury in rabbits. In the present study, we investigated whether the combination of IGF-1 and EPO protects against ischemic spinal cord injury in rabbits. METHODS: Animals were assigned to 1 of 4 groups (n = 6 in each): a control group (saline), an IGF-1 group (IGF-1 0.3 mg/kg), an EPO group (EPO 800 U/kg), or an IGF-1 + EPO group (IGF-1 0.3 mg/kg + EPO 800 U/kg). Spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. Saline, IGF-1, and EPO were administered intravenously just after the start of reperfusion. Hindlimb motor function was assessed daily for 7 days, after which histopathological evaluation was performed. To analyze phosphorylation of signal transduction molecules, animals were assigned to 1 of the 4 groups (n = 8 in each). Spinal cord ischemia and the treatment were the same as those described above. The spinal cords were removed at 15 or 30 min after reperfusion and used to analyze phosphorylation of signal transduction molecules. Four animals served as the preischemic control, and the spinal cord was removed just before the start of ischemia. RESULTS: In the IGF-1 + EPO group, both neurological and histopathological outcomes were significantly improved as compared to the control group, which was consistent with the increase of Janus kinase-2 (JAK2) phosphorylation. CONCLUSIONS: The combination of IGF-1 and EPO protects against ischemic spinal cord injury in rabbits. JAK2 might contribute to the protective effect.
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