5 research outputs found
Faim2 contributes to neuroprotection by erythropoietin in transient brain ischemia
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 Fasâapoptotic 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 phosphatidylinositolâ3 kinase/Akt (PI3K/Akt) pathway, which regulates Faim2 expression. Therefore, upâregulation of Faim2 may contribute to neuroprotection by EPO. Male Faim2âdeficient mice (Faim2â/â) and wildâtype 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 Faim2â/â animals administration of lowâdose EPO did not result in a significant reduction in stroke volume. Faim2 expression as measured by quantitative reverse transcription polymerase chain reaction (qRTâPCR) increased after lowâdose 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 postâmortem brain Faim2 displayed a differential expression in areas of penumbral ischemia. Faim2 upâregulation may contribute to the neuroprotective effects of lowâdose erythropoietin in transient brain ischemia. The doseâdependency may explain mixed effects of erythropoietin observed in clinical stroke trials