RESUMO
Overproduction of reactive oxygen species (ROS) and inflammation are two key pathogeneses of noise-induced hearing loss (NIHL), which leads to outer hair cell (OHC) damage and hearing loss. In this work, we successfully developed ROS-responsive nanoparticles as berberine (BBR) carriers (PL-PPS/BBR) for OHC-targeted therapy of NIHL: Prestin-targeting peptide 2 (PrTP2)-modified nanoparticles (PL-PPS/BBR), which effectively accumulated in OHC areas, and poly(propylene sulfide)120 (PPS120), which scavenged ROS and converted to poly(propylene sulfoxide)120 in a ROS environment to disintegrate and provoke the rapid release of BBR with anti-inflammatory and antioxidant effects. In this study, satisfactory anti-inflammatory and antioxidant effects of PL-PPS/BBR were confirmed. Immunofluorescence and scanning electron microscopy (SEM) images showed that PL-PPS/BBR effectively accumulated in OHCs and protected the morphological integrity of OHCs. The auditory brainstem response (ABR) results demonstrated that PL-PPS/BBR significantly improved hearing in NIHL guinea pigs after noise exposure. This work suggested that PL-PPS/BBR may be a new potential treatment for noise-associated injury with clinical application.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Berberina/farmacologia , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Espécies Reativas de Oxigênio/química , Animais , Anti-Inflamatórios não Esteroides/química , Antioxidantes/química , Berberina/química , Modelos Animais de Doenças , Portadores de Fármacos/química , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Cobaias , Estrutura Molecular , Nanopartículas/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Propriedades de SuperfícieRESUMO
OBJECT: Acoustic stimulation induced LTP in the human auditory cortex was successfully recorded for the first time by electroencephalography (EEG) using a stimulus of 1 kHz pure-tone in 2005. However, it was barely reproduced, given considerable challenges to reliably elicit and accurately record the enhanced potentials in vivo. The purpose of this paper was to explore whether acoustic stimuli other than 1 kHz pure-tone could generate LTP or not. MEASURES: To answer this question, we proposed a tetanic-stimulation paradigm of pure-tones, narrow-band noises (NBNs) and white noise (WN) to elicit LTP in human subjects. RESULTS: The results showed that pure-tones with different frequency could elicit LTP in human auditory cortex, and proved for the first time that NBNs and WN could also achieve the same goal. Interestingly, it was also shown that the noises with certain bandwidth induced the greatest LTP and the WN induced LTP had the least variation over time and across subjects in comparison with pure-tones and NBNs. CONCLUSIONS: In light of the results, we suggested to use the paradigm for broader studies of human in vivo cortical plasticity.