Recombinant human erythropoietin prevents ischemia-induced apoptosis and necrosis in explant cultures of the rat organ of Corti.

Abstract

This study was designed to evaluate the effect of recombinant human erythropoietin (rhEPO), insulin-like growth factor-1 (rhIGF-1) and epidermal growth factor (rhEGF) on ischemia-induced hair cell loss in an organotypic cochlea culture. The apical, middle and basal parts of the organs of Corti (newborn rat, postnatal days 3-5) were exposed to ischemia (3.5 h) in glucose-free artificial perilymph (pO2 10-20 mmHg) with or without growth factors. Controls were exposed to normoxia. Twenty-four hours after the onset of ischemia, the cultures were stained using tetramethyl rhodamine isothiocyanate (TRITC) phalloidin (hair cells), propidium iodide (membrane integrity) and apoptosis detection kit (DNA-fragmentation). Ischemia (3.5 h) induced a hair cell loss of 20 and 40% in the middle and basal cochlear parts, respectively, and an increase of the numbers of PI-stained and DNA-fragmented nuclei (controls 0-1, ischemia 4-7 nuclei/100 microm). The basal part was more affected than the apical one. rhEPO and rhIGF-1 significantly attenuated the ischemia-induced hair cell loss by reducing processes involved in apoptosis and necrosis. rhEPO has been in clinical use for more than a decade and found to be well tolerated. Therefore, rhEPO could be an effective drug for the prevention of hearing loss via a hair cell protective mechanism.

• Authors: Nadezhda Andreeva, Amarjargal Nyamaa, Heidemarie Haupt, Johann Gross, Birgit Mazurek
• Journal: Neuroscience letters (Neurosci Lett) Vol. 396 Issue 2 Pg. 86-90 (Mar 27 2006) ISSN: 0304-3940 [Print] Ireland
• PMID: 16332412 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Erythropoietin
• Epidermal Growth Factor
• Insulin-Like Growth Factor I

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Epidermal Growth Factor (genetics, pharmacology)
• Erythropoietin (genetics, pharmacology)
• Hair Cells, Auditory (blood supply, drug effects, pathology)
• Humans
• In Vitro Techniques
• Insulin-Like Growth Factor I (genetics, pharmacology)
• Ischemia (complications, pathology)
• Necrosis (pathology, prevention & control)
• Organ of Corti (blood supply, drug effects, pathology)
• Rats
• Recombinant Proteins (administration & dosage)