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Erythropoietin reduces perihematomal inflammation and cell death with eNOS and STAT3 activations in experimental intracerebral hemorrhage

Cited 111 time in Web of Science Cited 112 time in Scopus
Authors
Lee, Soon-Tae; Chu, Kon; Sinn, Dong-In; Jung, Keun-Hwa; Kim, Eun-Hee; Kim, Se-Jeong; Kim, Jeong-Min; Ko, Song-Yi; Kim, Manho; Roh, Jae-Kyu
Issue Date
2006-03-17
Publisher
Blackwell Publishing
Citation
J Neurochem. 2006 Mar;96(6):1728-39.
Keywords
AnimalsApoptosis/drug effects/physiologyBiological Markers/metabolismBody Water/drug effects/physiologyBrain/drug effects/metabolism/physiopathologyBrain Edema/drug therapy/etiology/physiopathologyCell Death/drug effects/physiologyCerebral Hemorrhage/complications/*drug therapy/physiopathologyDisease Models, AnimalDose-Response Relationship, DrugEncephalitis/*drug therapy/etiology/physiopathologyEnzyme Activation/drug effects/physiologyEnzyme Inhibitors/pharmacologyErythropoietin/*pharmacology/therapeutic useMaleNG-Nitroarginine Methyl Ester/pharmacologyNerve Degeneration/*drug therapy/etiology/physiopathologyNitric Oxide Synthase Type III/*drug effects/metabolismRatsRats, Sprague-DawleyRecovery of Function/drug effects/physiologySTAT3 Transcription Factor/*drug effects/metabolismSignal Transduction/drug effects/physiologyTreatment Outcome
Abstract
Erythropoietin (EPO), a pleiotropic cytokine involved in erythropoiesis, is tissue-protective in ischemic, traumatic, toxic and inflammatory injuries. In this study, we investigated the effect of EPO in experimental intracerebral hemorrhage (ICH). Two hours after inducing ICH via the stereotaxic infusion of collagenase, recombinant human EPO (500 or 5000 IU/kg, ICH + EPO group) or PBS (ICH + vehicle group) was administered intraperitoneally, then once daily afterwards for 1 or 3 days. ICH + EPO showed the better functional recovery in both rotarod and modified limb placing tests. The brain water content was decreased in ICH + EPO dose-dependently, as compared with ICH + vehicle. The effect of EPO on the brain water content was inhibited by N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg). Mean hemorrhage volume was also decreased in ICH + EPO. EPO reduced the numbers of TUNEL +, myeloperoxidase + or OX-42 + cells in the perihematomal area. In addition, EPO reduced the mRNA level of TNF-alpha, Fas and Fas-L, as well as the activities of caspase-8, 9 and 3. EPO treatment showed up-regulations of endothelial nitric oxide synthase (eNOS) and p-eNOS, pAkt, pSTAT3 and pERK levels. These data suggests that EPO treatment in ICH induces better functional recovery with reducing perihematomal inflammation and apoptosis, coupled with activations of eNOS, STAT3 and ERK.
ISSN
0022-3042 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16539688

http://hdl.handle.net/10371/11879
DOI
https://doi.org/10.1111/j.1471-4159.2006.03697.x
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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