Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus.

To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential.

The application of SFDI and LSI system to evaluate the blood perfusion in skin flap mouse model.

The aim of this study is to evaluate whether the blood perfusion to tissues for detecting ischemic necrosis can be quantitatively monitored by spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) in a skin flap mouse model. Skin flaps were made on Institute of Cancer Research (ICR) mice. Using SFDI and LSI, the following parameters were estimated: oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), total hemoglobin (THb), tissue oxygen saturation (StO2), and speckle flow index (SFI). Histologically, epithelium thickness, collagen deposition, and blood vessel count of skin flap tissues were analyzed. Then, the correlation of SFDI and histological results was assessed by application of Spearman rank correlation method. As the result, the number of blood vessels and the percentage of collagen areas showed significant difference between the necrotic tissue group and the non-necrotic one. Especially, the necrotic tissue had a complete epithelial loss and loses its normal structure. We identified that SFDI/LSI parameters were significantly different between non-necrotic and necrotic tissue groups. Especially, all SFDI and LSI parameters measured on the 1st day after surgery showed significant difference between necrotic tissue and non-necrotic tissue. In addition, the number of blood vessel and percentage of collagen area were positively correlated with HbO2 and StO2 among SFDI/LSI parameters. Meanwhile, the number of blood vessel and percentage of collagen area showed the negative correlation with Hb. By applying SFDI and LSI simultaneously to the skin flap, we could quantitatively monitor the blood perfusion and the tissue condition which can help us to detect ischemic necrosis objectively in early stage.

Neuroprotective Effect of Valproic Acid on Salicylate-Induced Tinnitus.

High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca2+ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein-an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNFα and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.