Study on the Neuroprotection and Mechanism of C - EPO and EPO in MCAO Mice Models

Background: Brain ischemia can be treated using two methods, namely thrombolysis and neuroprotection. The therapeutic time window for thrombolysis is less than 6 h, while that for most neuroprotective agents ranges from several hours to several weeks. Many stroke survivors can profit from neuroprotective treatment. Erythropoietin (EPO) is an interesting candidate neuroprotective agent in human patients with acute ischemic stroke, in addition to playing a role in red blood cell propagation. Carbamylated EPO (C-EPO) plays no role in red blood cell propagation, and its underlying mechanism of action in neuroprotection is unknown. Objective: To understand the mechanisms underlying the neuroprotective effects of EPO and C-EPO in stroke. Methods: Twenty one male mice with a Middle Cerebral Artery Occlusion (MCAO) were equally divided into 3 subgroups (n = 7 per subgroup): A1: MCAO; A2: 2500U/ kg EPO-MCAO; A3:C-EPO 25 μg/kg. MCAO models were developed by introducing a silicon-coated nylon monofilament into the common carotid artery and distally advancing it by 9 mm toward the carotid bifurcation. Ninety minutes following reperfusion, the behavior of the mice was observed. Finally, the mice from all the groups were decapitated, their brains were removed and sectioned, and the sections were stained with cresyl violet. Western blotting and immunohistochemistry were used to measure the expression of the IP3, ERK1/2, JNK, P38, JAK, STAT5, BCL-XL, and Caspase3. Results: EPO and C-EPO increased the BCL-XL protein expression and decreased the Caspase3 protein expression in different manners. EPO can reduce apoptosis through activating IP3, MAPK, and JAK-STAT pathways, while C-EPO can reduce apoptosis only by activating the IP3 pathway. Conclusion: EPO and C-EPO play a role in neuroprotection in the MCAO mouse model through similar mechanisms, possibly mediated by the modulation of the IP3 pathway. *Corresponding author: Zan Wang, Neurology Department, the first hospital of Jilin university, 71 Xinmin Street, Changchun, Jilin, 130021, P. R. China, Tel: +8643188782378, Fax: +8643188782378; E-mail: [email protected] Received Date: May 09, 2017 Accepted Date: July 10, 2017 Published Date: July 11, 2017