Intranasal erythropoietin protects granular cells and reduces astrogliosis in the dentate gyrus after ischemic damage, an effect associated with molecular changes in erythropoietin and its receptor

Abstract

Within the hippocampus, the CA1 and dentate gyrus (DG) regions are considered the most and the least susceptible to damage by cerebral ischemia, respectively. In addition, it has been tested that rHuEPO exhibits neuroprotective properties. This work investigates the effect of different intranasal doses of rHuEPO, applied in different ischemic post-damage times in the DG, and the effect of the rHuEPO on astroglial reactivity after cerebral ischemia. Additionally, an effective dose for neuroprotection and an administration time was used to evaluate gene and protein expression changes of EPO and EPOR in the DG region. We observed a considerable loss of cells on the granular layer and an increased number of GFAP immunoreactive cells in this region only 72 h after the onset of ischemia/damage. When rHuEPO was administered, the number of morphologically abnormal cells and immunoreactivity decreased. In the analysis of protein and gene expression, there is no correlation between expression level of these molecules, although the rHuEPO amplifies the response to ischemia of EPO and EPOR gene for each evaluated time; in the case of the protein only at 2 h this effect was observed. We demonstrated the susceptibility of the DG to ischemia; so granular cells damage was observed, moreover of the astrocytic response, which is accompanied by molecular changes in signaling mediated by rHuEPO intranasal administration.

Keywords: Cerebral ischemia–reperfusion; Correlation mRNA/protein; Dentate gyrus susceptibility; Intranasal administration; Reactive astrocyte.