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Title: Neuroprotection by erythropoietin
Author: Cervellini, Ilaria
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2012
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Erythropoietin (EPO) is an erythropoietic cytokine that is also neuroprotective in vitro and in vivo. Neither the mechanism of action of EPO in neuroprotectio, nor the receptor involved is completely known. In fact, EPO regulates erythropoiesis by the homodimeric EPO receptor (EPOR)2. Variants of EPO, not binding (EPOR)2, are still neuroprotective, therefore another receptor may mediate this effect. In vivo, EPO is anti-inflammatory in several models of disease but, to date, a direct anti- inflammatory effect in vitro has not been clearly found. The focus of this thesis work was a twofold. Firstly, a direct anti-inflammatory effect of EPO was investigated in vitro. It was confirmed that EPO did not have any effect on production of cytokines induced by LPS. In addition, EPO did not reduce cytokines induced by alarmins and other inflammatory stimuli. EPO did not inhibit the pro-inflammatory receptor TREM-1. Finally, EPO did not act as anti-inflammatory by mobilization of endothelial precursor cells in vivo. The second focus of this thesis work was the study of a possible role of EPO on myelination by analysing the induction of myelin genes during differentiation of an oligodendrocyte cell line. EPO upregulated myelin gene expression (MaG and MBP), as studied by qPCR and Western Blot. EPOR was required for the effect of EPO, observed only in cells overexpressing EPOR. EPO induced high levels of the early growth response gene EGR2 that was however not involved in myelin gene induction. Finally, EPO was unable to induce myelin genes in an in vivo model of demyelination induced by cuprizone, neither at the peak of demyelination (3 and 5 weeks) nor during the recovery phase. Greater understanding of effects and mechanisms of action of EPO in the CNS would be useful to find new therapies promoting repair, for instance in diseases like MS in which no drug is available for that purpose.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: A000 Medicine