Neuroprotective effects of MK-801 on auditory cortex in salicylate-induced tinnitus: Involvement of neural activity, glutamate and ascorbate

Xiong, Shiqin; Song, Yu; Liu, Junxiu; Du, Yali; Ding, Yujing; Wei, Huan; Bryan, Kevin; Ma, Furong; Mao, Lanqun

doi:10.1016/j.heares.2019.01.021

Cited by 18 publications

(15 citation statements)

References 60 publications

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“…Based on these findings, researchers have attempted to investigate the therapeutic effects of AA during tinnitus, which might result from the abnormal generation of reactive oxygen species (ROS) after noise exposure and other etiologies; however, the results have been controversial and the mechanism has not been revealed. We found that the extracellular AA level in the AC significantly increased starting 1.5 hours after SS injection, which was in accordance with the results reported by other studies . In addition, this increase could be inhibited by lidocaine treatment, which currently represents the most effective treatment for tinnitus.…”

Section: Discussionsupporting

confidence: 92%

“…In our study, we treated rats with a high dose of SS (350 mg/kg) to investigate changes in the AC during tinnitus. This dose was the same as that used by Jastrboff and has been used in many behavioral experiments, with a reliable behavioral manifestation of tinnitus …”

Section: Discussionmentioning

confidence: 99%

“…Considering that AA also plays an important role in the transmission and clearance of glutamate, a common excitatory neurotransmitter in the brain, we suggested that SS injections may induce a neurotransmitter imbalance in the AC, which may cause tinnitus. An overload of glutamate has been found in the AC of tinnitus animal models and in the AC of humans, and the increased glutamate concentration could be weakened by glutamate antagonist MK‐801. Changes in gamma‐aminobutyric acid (GABA), another neurotransmitter associated with glutamate metabolism, have also been identified in the AC and other regions of the central auditory system .…”

Section: Discussionmentioning

confidence: 99%

“…This dose was the same as that used by Jastrboff and has been used in many behavioral experiments, with a reliable behavioral manifestation of tinnitus. 21,[23][24][25] AA reaches the highest concentration in the brain. 12 As an important endogenous antioxidant, SS is considered to be neuroprotective.…”

Section: Effects Of Lidocaine On Ss-induced Single-unit Ac Neuron Dismentioning

confidence: 97%

“…We found that the extracellular AA level in the AC significantly increased starting 1.5 hours after SS injection, which was in accordance with the results reported by other studies. 25 In addition, this increase could be inhibited by lidocaine treatment, which currently represents the most effective treatment for tinnitus. This result implied that AA might play some role in the generation of SS-induced tinnitus.…”

Section: Effects Of Lidocaine On Ss-induced Single-unit Ac Neuron Dismentioning

confidence: 99%

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Salicylate increased ascorbic acid levels and neuronal activity in the rat auditory cortex

Duan

Zhang

2019

Pediatric Investigation

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Importance Clinical observations have implied a central origin for tinnitus and potential therapeutic effects of ascorbic acid (AA); however, the detailed mechanisms remain undetermined. Objective To investigate changes in the AA levels and neural activity in the auditory cortex (AC) during salicylate‐induced tinnitus. Methods Rats were randomly divided into 3 groups: (1) saline group, which received an intraperitoneal saline injection; (2) SS group, which received an intraperitoneal sodium salicylate (SS) injection (350 mg/kg); and (3) SS+Lido group, which received an intraperitoneal SS injection (350 mg/kg) and lidocaine delivered to the AC by microdialysis. For each group, we firstly used an in vivo microdialysis technique to investigate the concentrations of AA in the AC; and secondly, we recorded the neural activity in the AC using a single‐unit recording technique. Results The AA concentration in the SS group significantly increased after SS injection, whereas that of the saline group did not change. The AA concentration in the SS+Lido group also showed an increasing trend but was significantly lower than that in the SS group. In the electrophysiological study, the spontaneous firing rate of the SS group was significantly higher than that of the saline group. In addition, the proportion of short interval discharges was also higher in the SS group than in the saline group. Both differences were reversed by lidocaine treatment. Interpretation Our data suggest that the elevation of AA levels in the AC may be related to increased neuronal activity, which may represent the mechanism underlying salicylate‐induced tinnitus.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Effects Of Lidocaine On Ss-induced Single-unit Ac Neuron Dismentioning

confidence: 97%

Section: Effects Of Lidocaine On Ss-induced Single-unit Ac Neuron Dismentioning

confidence: 99%

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Salicylate increased ascorbic acid levels and neuronal activity in the rat auditory cortex

Duan

Zhang

2019

Pediatric Investigation

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Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss

Fan,

Guan,

Zhong

et al. 2023

Advanced Science

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Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole‐brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate‐induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high‐gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.

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Neuroprotective effects of MK-801 against cerebral ischemia reperfusion

Yaghoobi,

Ataei,

Riahi

et al. 2024

Heliyon

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Neuroprotective effects of MK-801 on auditory cortex in salicylate-induced tinnitus: Involvement of neural activity, glutamate and ascorbate

Cited by 18 publications

References 60 publications

Salicylate increased ascorbic acid levels and neuronal activity in the rat auditory cortex

Salicylate increased ascorbic acid levels and neuronal activity in the rat auditory cortex

Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss

Neuroprotective effects of MK-801 against cerebral ischemia reperfusion

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