title: Different expression patterns of Ngb and EPOR in the cerebral cortex and hippocampus revealed distinctive therapeutic effects of intranasal delivery of Neuro-EPO for ischemic insults to the gerbil brain.
abstract: The purpose of this study was to evaluate the neuroprotective effects of intranasally delivered recombinant human neuronal erythropoietin (Neuro-EPO) on brain injury induced by unilateral permanent ischemia in the Mongolian gerbil. Expression of EPO receptor (EPOR) and neuroglobin (Ngb) over 5 weeks after intranasal treatment with Neuro-EPO was determined using immunohistochemistry. Mortality of Neuro-EPO-treated gerbils decreased after surgery, and the sensory and motor function was significantly improved. Histopathological mapping showed that Neuro-EPO significantly reduced delayed neuronal death in the brain. Expression of Ngb was upregulated in the cerebral cortex at most time points (expect for 10 min and 48 hr) and in the hippocampus at 10 min and from 48 hr to 5 weeks, whereas EPOR was almost downregulated or unchanged in the brain (expect for 48 hr). The 10 min and 48 hr seemed to be two time points for the brain to switch the expression of both Ngb and EPOR to early and late recovery phase, respectively. In addition, there were two phases, 10 min to 1 hr and 24 hr to 72 hr, respectively, closing to the "golden hour" of about 60 min and the "silver day" of 1 to 3 days, for the brain to recover from stroke onset with intranasal Neuro-EPO treatment. Therefore, the results suggest that the intranasal administration of Neuro-EPO is effective in the treatment of acute brain ischemia. The different expression patterns of Ngb and EPOR is probably due to ischemic tolerance in the cerebral cortex and ischemic sensitivity in the hippocampus.
authors.affiliation: Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Yuneidis
authors.initials: Y
authors.lastname: Mengana
authors.forename: Yamila Rodríguez
authors.initials: YR
authors.lastname: Cruz
authors.forename: Adriana
authors.initials: A
authors.lastname: Muñoz
authors.forename: Iliana Sosa
authors.initials: IS
authors.lastname: Testé
authors.forename: Jorge Daniel
authors.initials: JD
authors.lastname: García
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wu
authors.forename: Julio César García
authors.initials: JC
authors.lastname: Rodríguez
authors.forename: Chenggang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects*; D005849:Gerbillinae; D005914:Globins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009928:Organ Specificity; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D011994:Recombinant Proteins; D013997:Time Factors
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D005914:Globins