Neuroprotective effect of erythrcpoietin

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: University of Tsukuba
• Principal Investigator: YANAKA Kiyoyuki University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (10312307)
• Co-Investigator(Kenkyū-buntansha): MUKAI Harumi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (80323301) ; NAGASE Sohji University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (10189128)
• Project Period (FY): 2003 – 2004
• Keywords: cerebral ischemia / cerebral infarction / erythropoietin

Research Abstract

Erythropoietin(EPO) was originally identified as the principal regulator of erythroid progenitor cells, which are responsible for the formation of red blood cells. Circulating EPO binds to its receptor(EPOR) expressed on erythroid progenitor cells and results in the stimulation of erythropoiesis. The induction of erythropoiesis yields a progressive improvement in the supply of oxygen to tissue. In addition to promoting the survival, proliferation, and differentiation of immature erythroid cells, erythropoietin and the erythropoietin receptor have recently been shown to modulate cellular signal transduction pathways that extend beyond the erythropoietic function of erythropoietin. More recent work has begun to elucidate the role of EPO and its receptor in the brain. In particular, work that has demonstrated the production of EPO and the expression of the EPOR in brain tissue strongly suggests a significant role for EPO in the central nervous system(CNS). In particular, erythropoietin has been linked to the prevention of programmed cell death in neuronal systems. Although this work is intriguing, the underlying molecular mechanisms that serve to mediate neuroprotection by erythropoietin are not well understood. The aim of the proposed study is to demonstrate the neuroprotective effect of EPO in a transgenic mouse model of focal cerebral ischemia. New knowledge of the cellular pathways regulated by erythropoietin in neuronal environments will potentially solidify the development and initiation of therapeutic strategies against nervous system disorders. We tested the neuroprotective effect of EPO by measuring apoptosis and vascular-endothelial growth factor in a knockout mouse model of transient focal and global ischemia models. The number of experimental animals who survived after surgery was not large enough to reach statistical analysis. However, there was a tendency in neuroprotective effect of EPO. Further investigation with larger animals is needed.