EFFECT OF IBUDILAST ON MICROCIRCULATION THROMBOSIS IN RAT INNER-EAR

The effect of ibudilast (0. 1, 0.3 mg/kg), which has cerebral vasodilating and antiplatelet effects, was evaluated in two models of rat inner ear microcirculation thrombosis by using the photochemical reaction between green light (wave length: 540 nm) and intravenous injection of rose bengal. Furthermore, the inner ear blood flow was measured by a laser-Doppler flowmeter. In the hearing disturbance model, under anesthesia, the compound action potential of the cochlear nerve (AP) was measured by an electrocochleogram. The sound stimulus was an 8-kHz sine wave at 80 dB SPL. The AP was calculated 128 times. In the controls, the AP disappeared about 4 min after the intravenous injection of rose bengal (20 mg/kg). The time required to completely suppress the AP in the animals treated with ibudilast (0.1, 0.3 mg/kg) was significantly prolonged as compared with that in the controls. In the equilibrium dysfunction model, ibudilast (0.1, 0.3 mg/kg) reduced the time of abnormal swimming in the swimming test 24 hr after the completion of photo-illumination. Ibudilast (0.3 mg/kg) increased the inner ear blood flow during the 10-min observation period as compared with the controls, while it did not affect the mean blood pressure. In conclusion, ibudilast increased the inner ear blood flow and was effective in two models of rat inner ear microcirculation thrombosis.