Investigation of hearing loss and the effect of erytropoietin in the newborn rats with hypoxic-ischemia induced encephalopathy

Objective: To investigate the effect of hypoxic-ischemia on the hearing and otoprotective effect of recombinant erythropoietin.Materials and Methods: Twenty eight seven-day Wistar albino rat pups were divided into four groups: Control group (n=8), sham group (n=5), hypoxic- ischemic encephalopathy group (n=8), recombinant erythropoietin treated group (n=7). Control group were injected intraperitoneal serum physiologic, sham group had only neck incision without carotid ligation and intraperitoneal serum physiologic, Hypoxic ischemic encephalopathy group and recombinant erythropoietin treated group were subjected to left common carotid artery ligation followed by 2.5 hour hypoxic exposure to a mixture of 8%oxygen ,92% pure nitrogen. Hypoxic ischemic encephalopathy group were injected intraperitoneal serum physiologic and recombinant erythropoietin treated group received eryhthropoietin 1000units/kg within the same volum as serum physiologic. At seventh week hearing of the animals were evaluated by click ABR, 6 kHz and 8 kHz tone burst stimuli. Animals sacrified and both temporal lobes, cochleas and brainstems of the animals were collected. Tissue samples were evaluated with light microscopy, immunuhistochemical studies such as TUNEL and caspase-3 stainings and electron microscopy.Results: Hearing was detoriated in hypoxic-ischemic encephalopathy group animals, in some of the rats hearing loss were bilateral. In recombinant erythropoietin treated group ; ABR values were close to controls. Difference between hypoxic ischemic encephalopathy group and ertyhropoietin treated group were statistically significant (p<0.05). Hypoxic ischemic encephalopathy is found to cause apoptotic changes within brainstem shown by light microscopy and immunohistochemical methods. Apoptotic changes also were found within the organ of Corti, spiral ganglion cells and neurons of temporal lobe by electron microscopic investigation. In recombinant erythropoietin treated group most of those apoptotic changes were found to be decreased.Conclusion: Hypoxic-ischemic encephalopathy leads to hearing loss by inducing apoptotic pathways of the hearing system and recombinant erythropoietin is found to prevent those effects.