To test liposome-encapsulated hemoglobin (LEH) in transient cochlear ischemia/reperfusion as a model of sudden deafness, Mongolian gerbils were randomly assigned to receive 2 mL/kg of either low-affinity LEH (l-LEH, P₅₀0₂ = 40 mm Hg), high-affinity LEH (h-LEH, P₅₀0₂ = 10 mm Hg), homologous red blood cells (RBCs), or saline (each group n = 6) 30 min before 15-min occlusion of the bilateral vertebral arteries and reperfusion. Sequential changes in hearing were assessed by auditory brain response 1, 4, and 7 days after ischemia/reperfusion, when the animals were sacrificed for pathological studies. h-LEH was significantly more protective than l-LEH in suppressing hearing loss, in contrast to RBC or saline treatment, at 8, 16, and 32 kHz, where hearing loss was most severe (P < 0.05 between any two groups) on the first day after cochlear ischemia/reperfusion. Thereafter, hearing loss improved gradually in all groups, with a significant difference among groups up to 7 days, when morphological studies revealed that the inner hair cells but not the outer hair cells, were significantly lost in the groups in the same order. The results suggest that pretreatment with h-LEH is significantly more protective than l-LEH in mitigating hearing loss and underlying pathological damage, in contrast to transfusion or saline infusion 7 days after transient cochlear ischemia/reperfusion.
This study was designed to investigate the protective effects of recombinant human insulin-like growth factor 1 (rhIGF1), applied locally via a hydrogel, against ischemic damage of the cochleae in gerbils. A hydrogel was immersed in rhIGF1 or saline and was applied on the round window membrane 30 min after the ischemia. Local rhIGF1 treatment significantly reduced the elevation of auditory brain responses thresholds at a frequency of 8 kHz on days 1, 4, and 7 after ischemia. A histological analysis revealed increased survival of inner hair cells in the animals treated with rhIGF1 via the hydrogel 7 days after ischemia. These findings showed that local rhIGF1 application using a hydrogel has the potential to protect the cochleae from ischemic injury.
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