Exploring the neuroprotective effects of resveratrol in a rat model of hearing loss using 4-[18F]-ADAM/small animal PET

Objectives Noise-induced hearing impairment may affect brain serotoninergic system. The purpose of this study was to investigate the effect of resveratrol against noise-induced serotonergic abnormality in rat brain using 4-[18F]-ADAM (a serotonin transporter imaging agent) and small small animal-PET.

Methods Male Sprague Dawley rats were exposed to an 8 kHz noise at 116 dB sound pressure level for 3.5 h. The resveratrol(30mg/kg) was injected intraperitoneally before the noise exposure and once per day for 4 successive days. The 4-[18F]-ADAM/small animal PET and auditory brainstem response test were performed at 1 day, 1 week, and 4weeks after the noise exposure. The specific uptake ratios (SURs) of 4-[18F]-ADAM/small animal PET were determined in the midbrain, hypothalamus, thalamus, striatum, frontal cortex of the rats. Additional groups of rats were performed immunohistochemistry and surface preparation of the cochleae 5 days after the noise exposure, respectively.

Results At 1 day and 1 week after the noise exposure without resveratrol treatment, the SURs of 4-[18F]-ADAM were significantly decreased in all brain regions of rats. However, at 4 weeks after the noise exposure, the SURs of 4-[18F]-ADAM recovered to normal values. The SURs of 4-[18F]-ADAM in the rats with resveratrol treatment was significantly higher than those of without resveratrol-treated rats in the all brain regions at 1 day and 1 week after the noise exposure. The results of serotonin transporters (SERTs) immunohistochemistry were comparable to those of the PET imaging in the various brain regions.

Conclusions These results suggest that resveratrol may provide neuroprotective effects against noise-induced serotonergic abnormality and the 4-[18F]-ADAM coupled with small animal PET may be feasible to monitor the status of SERTs in the therapeutic progress.