Effects of erythropoietin and its receptor on nervous system

Ping Wang; Wei Zhou

摘要：OBJECTIVE: To investigate the effects of erythropoietin (EPO) and its receptor (EPOR) on nervous system, and its possible mechanism.DATA SOURCES: By inputting the key words "erythropoietin ,nervous system", we performed a search of Medline for English articles, which were published during September 1996 to August 2006, about EPO and EPOR in nervous system.STUDY SELECTION: The materials were selected firstly, literatures were chosen for treatment group and control group and those obviously non-randomized studies were excluded. The full texts of the left literatures were searched. Inclusive criteria: ① Randomized controlled study. ②Experimental or clinical studies (parallel control group included). ③Treatment group was recombinant human erythropoietin(rHuEPO)-treated group. Exclusive criteria: repetitive study.DATA EXTRACTION: A number of 380 randomized or non-randomized articles about the effect of EPO on nervous system were collected, and 49 experiments or clinical trials met the inclusive criteria. Among 331 exclusive articles, 237 were non-randomized or repetitive studies and 94 were review articles. DATA SYNTHESIS: Forty-nine experiments or clinical trials confirmed that EPO and EPOR were expressed in the central nervous system (CNS) and peripheral nervous system(PNS) of gnawer, primate and human being; rHuEPO had obvious neuroprotective effects on brain hypoxia, brain ischemia, experimental intracranial hemorrhage, brain trauma, experimental autoimmune encephalomyelitis, human immunodeficiency virus (HIV)-related sensory neuropathy, distal axonopathy, experimental diabetic neuropathy and acute spinal injury models. Its mechanism maybe involve anti-excitatory toxicity, preventing the production of nitric oxide (NO), lessening inflammatory reaction, resisting apoptosis, maintaining vascular integrity, promoting angiogenesis, promoting the proliferation and differentiation of neural stem cells and progenitor cells and so on. Exogenous EPO could be transported to brain tissues via blood brain barrier during the circulation. rHuEPO can be used for treatment of cerebral ischemia, cerebral anoxia, subarachnoid hemorrhage, brain trauma, spinal injury and other CNS or PNS diseases. Hypertension, poorly-developed red blood cells, non-fetal myocardial infarction, angiogenesis, thrombosis, fever, vomiting, short breath, paresthesia and upper respiratory tract infection were possibly found in long-term successive application of EPO. CONCLUSION: EPO has nerve growth promoting, neurotrophic and neuroprotective effects. It has been used for treatment of various nervous system diseases, but large-scale, multi-center clinical trials are needed for further research. EPO should be carefully used in clinical practice, and its effective dosage, indications, removal of EPO activity, EPQ derivate with potential toxicity and other related problems need further investigations.