ABSTRACT
OBJECTIVE: This study aimed to assess the correlation between the spontaneous nystagmus (SN) and the subjective visual vertical/horizontal (SVV/SVH) among patients with vestibular neuritis (VN) at the different head positions. STUDY DESIGN: Case-control study. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine. METHODS: This study evaluated the SVV/SVH in both healthy subjects and patients with VN. These evaluations were performed in 5 different head positions: upright, 45° tilt to the left, 90° tilt to the left, 45° tilt to the right, and 90° tilt to the right. Additionally, the intensity of SN, as measured by slow-phase velocity, was recorded. RESULTS: In patients with VN, a significant correlation was observed between SN and SVV/SVH in an upright position. The intensity of SN was higher when the head was tilted 90° toward the affected side compared to other positions. The SVV/SVH displayed an ipsiversive shift, when the head was tilted toward both the lesion and unaffected sides, exhibiting a contraversive direction. Furthermore, the changes in position-induced SN were consistent with the displacements of SVV and SVH caused by head tilt. CONCLUSION: The presence of SN in patients with VN was observed to vary across different head position. These variations could potentially be attributed to the diverse activation patterns of the mechanical properties of otolith organs that are induced by head tilts.
ABSTRACT
Cisplatin is an effective chemotherapeutic drug for different cancers, but it also causes severe and permanent hearing loss. Oxidative stress and mitochondrial dysfunction in cochlear hair cells (HCs) have been shown to be important in the pathogenesis of cisplatin-induced hearing loss (CIHL). CDGSH iron sulfur domain 1 (CISD1, also known as mitoNEET) plays a critical role in mitochondrial oxidative capacity and cellular bioenergetics. Targeting CISD1 may improve mitochondrial function in various diseases. However, the role of CISD1 in cisplatin-induced ototoxicity is unclear. Therefore, this study was performed to assess the role of CISD1 in cisplatin-induced ototoxicity. We found that CISD1 expression was significantly increased after cisplatin treatment in both HEI-OC1 cells and cochlear HCs. Moreover, pharmacological inhibition of CISD1 with NL-1 inhibited cell apoptosis and reduced mitochondrial reactive oxygen species accumulation in HEI-OC1 cells and cochlear explants. Inhibition of CISD1 with small interfering RNA in HEI-OC1 cells had similar protective effects. Furthermore, NL-1 protected against CIHL in adult C57 mice, as evaluated by the auditory brainstem response and immunofluorescent staining. Mechanistically, RNA sequencing revealed that NL-1 attenuated CIHL via the PI3K and MAPK pathways. Most importantly, NL-1 did not interfere with the antitumor efficacy of cisplatin. In conclusion, our study revealed that targeting CISD1 with NL-1 reduced reactive oxygen species accumulation, mitochondrial dysfunction, and apoptosis via the PI3K and MAPK pathways in HEI-OC1 cell lines and mouse cochlear explants in vitro, and it protected against CIHL in adult C57 mice. Our study suggests that CISD1 may serve as a novel target for the prevention of CIHL.
