Experimental evidence of the potential use of erythropoietin by intranasal administration as a neuroprotective agent in cerebral hypoxia
-
Amalia Merelli
,
Laura Caltana
Abstract
Stroke is a major human health problem without efficient available therapeutics. Ischemic brain injury can induce cell death as well as upregulation of endogenous adaptive mechanisms depending on the severity and duration of hypoxia, and the activity of transcription factors, such as hypoxia inducible factor 1-α (HIF-1α). HIF-1α induces gene expression as multidrug resistance (MDR-1) gene associated with drug-refractory phenotype, as well as erythropoietin (Epo) and erythropoietin receptor (Epo-R) associated with O2 supply. The spontaneous stimulation of the Epo/Epo-R system is not enough for brain protection. Therefore, administration of exogenous recombinant human Epo (rHu-Epo) was suggested as an alternative therapy in stroke. In several experimental models of brain hypoxia, Epo and Epo variants, including rHu-Epo, showed neuroprotective effects. Intranasal administration of these Epo-compounds can reach the central nervous system and protect the brain against ischemia, avoiding hematopoietic effects. However, it has been reported that high expression of Epo-R in neurons must be available to be activated by Epo. According to these considerations, intranasal delivery of rHu-Epo could be an interesting approach in the treatment of cerebral hypoxias avoiding both (i) adverse peripheral effects of treatment with Epo in stroke, and (ii) the pharmacoresistant phenotype depending on MDR-1 expression.
©2011 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- Editorial
- Ageing populations, complex diseases and their challenge to 21st century healthcare: the focus of the European Society for Pharmacogenomics and Theranostics
- Reviews
- Clopidogrel pharmacogenetics: metabolism and drug interactions
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- Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins
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