Theranostics 2021; 11(6):2522-2533. doi:10.7150/thno.49121

Research Paper

Neutrophils infiltrate into the spiral ligament but not the stria vascularis in the cochlea during lipopolysaccharide-induced inflammation

Seong Hoon Bae1, Jee Eun Yoo1, Young Ho Choe2,3, Sang Hyun Kwak1, Jae Young Choi1, Jinsei Jung1,3✉, Young-Min Hyun2,3 ✉#

1. Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
2. Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea.
3. Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.
#Primary correspondence should be addressed to this author.

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Citation:
Bae SH, Yoo JE, Choe YH, Kwak SH, Choi JY, Jung J, Hyun YM. Neutrophils infiltrate into the spiral ligament but not the stria vascularis in the cochlea during lipopolysaccharide-induced inflammation. Theranostics 2021; 11(6):2522-2533. doi:10.7150/thno.49121. Available from https://www.thno.org/v11p2522.htm

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Abstract

It has been challenging to apply intravital imaging for monitoring the inner ear, as the anatomical location and intricate structure hamper the access of imaging instruments to the inner ear of live mice. By employing intravital imaging of the cochlea in live mice with two-photon microscopy, we investigated neutrophil infiltration into the cochlea tissue and its characteristics under a lipopolysaccharide (LPS)-induced inflammatory state.

Methods: Cochlea inflammation was induced by LPS injection to the middle ear. Using two-photon intravital microscopy with specifically designed surgical exteriorization of the cochlea in live mice, we investigated the dynamic features of neutrophils in the lateral wall of the cochlea. The molecular expression pattern of the cochlea lateral wall was also investigated during the LPS-induce inflammation.

Results: Despite the contention of whether neutrophils are recruited to the spiral ligament (SL) during inflammation, we observed that LPS-induced inflammation of the middle ear, which mimics acute otitis media, triggered neutrophil migration to the SL in the lateral wall. Notably, massive neutrophil infiltration to the SL occurred 2 days after LPS inoculation, but there was no neutrophil infiltration into the stria vascularis (SV) region. At 1 day after LPS-induced cochlear inflammation, increased mRNA expression of interleukin-1β, interleukin-6 were identified in both the SL and SV, while the ICAM-1 mRNA expression increased only in the SL. The differential reactivity of ICAM-1 is likely responsible for the different neutrophil recruitment pattern in the cochlea.

Conclusion: Intravital imaging of the cochlea revealed that neutrophil recruitment and infiltration during inflammation are spatially controlled and exclusively observed in the SL but not in the SV and organ of Corti.

Keywords: two-photon intravital imaging, neutrophil, cochlea, spiral ligament, stria vascularis