Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear / 神经科学通报·英文版

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.

Zonas mortas na cóclea em freqüências altas: implicações no processo de adaptação de prótese auditivas / Dead regions in the cochlea at high frequencies: implications for the adaptation to hearing aids

Em perdas auditivas de grau moderado a severo nas freqüências altas, a lesão coclear pode estar relacionada a "zonas mortas", regiões onde as células ciliadas internas e/ou neurônios adjacentes não são funcionais. OBJETIVO: Avaliar o reconhecimento de fala em pacientes com e sem zonas mortas na cóclea em freqüências altas. MATERIAL e MÉTODO: Estudo clínico e experimental de 30 indivíduos adultos, distribuídos em dois grupos: grupo 1 - 15 indivíduos sem zonas mortas, e grupo 2 - 15 com zonas mortas na cóclea. Os pacientes foram submetidos à pesquisa do índice de reconhecimento de fala, limiar de reconhecimento de sentenças, sem e com ruído competitivo. Os testes de fala foram realizados sem prótese, com próteses auditivas amplificando a faixa de freqüências de 100 a 8000 Hz (programa 1) e com amplificação restrita, 100 a 2560 Hz (programa 2). RESULTADOS: O grupo 1 apresentou melhor desempenho utilizando as próteses auditivas no programa 1. Já o grupo 2 obteve melhor desempenho com o programa 2. CONCLUSÕES: Pacientes sem zonas mortas na cóclea obtêm maior benefício com a amplificação em freqüências altas. Na presença de zonas mortas em freqüências altas, o melhor desempenho é obtido com a amplificação restrita nestas freqüências.

In patients with moderate to severe high-frequency hearing loss, cochlear damage may include "dead regions" where there are no functional inner hair cells and/or associated neurons. AIM: This study examines speech recognition in sensorineural impaired hearing patients with and without cochlear dead regions at high frequencies. METHODS: a clinical and experimental study was made of thirty patients with sensorineural hearing loss that were classified into two groups: group 1 - included 15 subjects with hearing loss and no dead regions; and group 2 - included 15 subjects with dead regions in the cochlea at high frequencies. Patients undertook word recognition score and speech reception threshold tests, with and without background noise. The speech tests were done with and without hearing aids in two situations: program 1 - broadband amplification (bandwidth 8000 Hz); and program 2 - amplification up to 2560 Hz, without high frequency gain. RESULTS: For subjects with no dead regions in the cochlea (group 1) performance improved with program 1. For subjects with dead regions in the cochlea (group 2) performance improved with program 2. CONCLUSIONS: Subjects with no dead regions in the cochlea benefited from high-frequency information. Subjects with dead regions in the cochlea benefited from reduced gain at high frequencies.