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ISCHEMIC TOLERANCE IN THE COCHLEA

Shoichiro Takeda, Tadashi Yoshida, Nobuhiro Hakuba, Jyun Hyodo, Kensuke Fujita, Ryuji Hata, Kiyofumi Gyo

Department of Otolaryngology, Ehime University School of Medicine, Shitukawa Toon-shi Ehime, Japan; Department of Otolaryngology, Osaka Red Cross Hospital, Fudegasaki-cho5-30 Tennohji-ku Osaka-shi Osaka, Japan; Department of Functional Histology, Ehime University School of Medicine, Shitukawa Toon-shi Ehime, Japan

OBJECTIVES: According to recent experimental studies of brain ischemia, neuronal cell death due to severe ischemia may be relieved by a preceding minor ischemia. This phenomenon is called ischemic tolerance, and is extensively studied in the brain and the heart. At present,there is no report that mentions this phenomenon in the cochlea. The aim of the present study is to reveal if such mechanism works in the cochlea using an animal model of transient cochlear ischemia.

METHODS: Adult male (60-80g) Mongolian gerbil was used in this study, since it lacks the posterior communicating arteries and the cochlea is nourished solely by the vertebral arteries. Cochlear ischemia was introduced in animals by occluding the bilateral vertebral arteries for 2-min as a preliminary minor ischemia or 15-min as a severe ischemia. Hearing was assessed sequentially by recording auditory brainstem responses (ABR). Our animal model features that the damage of the cochlea was severer at the basal turn, and that the inner hair cells (IHCs) were more fragile than the outer hair cells. In histological study, therefore, loss of IHC was counted in specimens stained with rhodamine-phalloidin and Hoechst 33342. The animals were divided into two groups; 1) single ischemia group (n=8, 16 ears), that was loaded with 15-min ischemia, and 2) double ischemia group (n=6, 12 ears), that was treated with 2-min ischemia 2 days before loading of 15-min ischemia. The results were compared between the two groups.

RESULTS: On the 7th day after 15-min ischemia, the average increases in ABR thresholds in single ischemia group and in double ischemia group were 23.4±8.9 dB and 12.9±9.4 dB, respectively. The increase in the latter group was significantly lower than that of the former group (p<0.01). At the basal turn, percentages of IHC loss in single ischemia group and in double ischemia group were 16.3±3.5% and 6.4±2.9%, respectively. The results were also statistically significant.

CONCLUSIONS: The present study clearly demonstrated ischemic tolerance phenomenon in the cochlea, although it remains unclear how it works in prevention of recurrent ischemic attack to the cochlea.