Faim2 contributes to neuroprotection by erythropoietin in transient brain ischemia.
J Neurochem
; 145(3): 258-270, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29315561
ABSTRACT
Delayed cell death in the penumbra region of acute ischemic stroke occurs through apoptotic mechanisms, making it amenable to therapeutic interventions. Fas/CD95 mediates apoptotic cell death in response to external stimuli. In mature neurons, Fas/CD95 signaling is modulated by Fas-apoptotic inhibitory molecule 2 (Faim2), which reduces cell death in animal models of stroke, meningitis, and Parkinson disease. Erythropoietin (EPO) has been studied as a therapeutic strategy in ischemic stroke. Erythropoietin stimulates the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway, which regulates Faim2 expression. Therefore, up-regulation of Faim2 may contribute to neuroprotection by EPO. Male Faim2-deficient mice (Faim2-/- ) and wild-type littermates (WT) were subjected to 30 min of middle cerebral artery occlusion (MCAo) followed by 72 h of reperfusion. EPO was applied before (30 min) and after (24 and 48 h) MCAo. In WT mice application of EPO at a low dose (5000 U/kg) significantly reduced stroke volume, whereas treatment with high dose (90 000 U/kg) did not. In Faim2-/- animals administration of low-dose EPO did not result in a significant reduction in stroke volume. Faim2 expression as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) increased after low-dose EPO but not with high dose. An extensive phenotyping including analysis of cerebral vessel architecture did not reveal confounding differences between the genotypes. In human post-mortem brain Faim2 displayed a differential expression in areas of penumbral ischemia. Faim2 up-regulation may contribute to the neuroprotective effects of low-dose erythropoietin in transient brain ischemia. The dose-dependency may explain mixed effects of erythropoietin observed in clinical stroke trials.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ataque Isquêmico Transitório
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Eritropoetina
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Proteínas Reguladoras de Apoptose
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Neuroproteção
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha