The primary death pathway of outer hair cells of rat cochlea following styrene exposure
- VernacularTitle:苯乙烯致耳蜗外毛细胞死亡的主要途径观察
- Author:
Weiping YANG
;
Bohua HU
;
Henderson DONALD
- Publication Type:Journal Article
- Keywords:
hearing loss;
styrene;
cochlea;
hair cells;
apoptosis;
necrosis
- From:
Medical Journal of Chinese People's Liberation Army
2001;0(07):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To compare the prevalence of apoptosis and necrosis, and investigate the primary death pathway of outer hair cells of rat cochlea following styrene exposure. Methods Fourteen adult Long Evans rats were used in the present study. The animals were randomly assigned into test group (n=8) and control group (n=6). Animals in test group were exposed to styrene by gavage at 400 mg/kg (2g styrene was mixed with 1ml olive oil). Treatment was performed once a day, 5 days per week for 3 weeks. Animals in control group were fed by gavage the same volume of olive oil on an identical time schedule used for the test group. The auditory brainstem response (ABR) thresholds of both ears elicited with clicks were measured before and at the end of the 3-week styrene or olive oil treatment. After hearing was re-assessed, animals were sacrificed and cochleae were quickly removed from the skull. Following fixation, whole specimens comprising the basilar membrane with Corti's organ were separated from the modiolus. Apoptotic, necrotic and missing outer hair cells (OHCs) were distinguished by combined assays of nuclear staining with propidium iodide (PI), TUNEL assay and filamentous actin(F-actin)staining with FITC-phalloidin. Each Corti's organ was thoroughly examined by fluorescence microscopy. The numbers of damaged OHCs (apoptotic, necrotic and missing OHCs) were documented. Results Neither threshold shift of ABR nor sign of hair cell (HC) damage was found in the cochlea of control animals. The animals of test group showed both physiological and pathological changes in the cochleae following the 3-week styrene treatment. ABR testing revealed an average of 15 dB of threshold shifts. F-actin staining exhibited the maximal level of OHCs damage in the middle portion of Corti's organ. The major damage occurred in the third row of OHCs, followed by the second and first rows of OHCs. Three types of morphological changes in damaged OHC nuclei were revealed by PI labeling: nuclear condensation, nuclear swelling and nuclear missing. Strong TUNEL green fluorescence appeared in the OHCs with condensed nuclei. Quantitative analysis showed that the average number of apoptotic OHCs was approximately three times greater than the number of necrotic OHCs (P=0.01). Conclusion It is indicated that apoptosis is the primary death pathway of OHCs leading to generation of the cochlear lesion following styrene exposure.
