Effectiveness of transcutaneous vagus nerve stimulation (tVNS) on salicylate-induced tinnitus.

INTRODUCTION: Tinnitus is the most common symptom of auditory system disorders. It affects the quality of life of millions of people, but it is still incurable in most cases. Vagus nerve stimulation (VNS) therapy is a potential new treatment for subjective tinnitus. In this study, transcutaneous vagus nerve stimulation (tVNS) combined with tones was utilized to treat salicylate-induced tinnitus since salicylate is a reliable and convenient approach for rapidly inducing tinnitus. METHODS: Wistar rats were divided into acoustic stimulation alone (AS, n = 6), tVNS alone (n = 6), and tVNS with AS (n = 6) groups for behavioral and electrophysiological tests. They were assessed by auditory brainstem response (ABR), prepulse inhibition (PPI), gap prepulse inhibition of the acoustic startle (GPIAS), social interactions, and aggressive behavior tests at baseline and seven days' post-salicylate (175 mg/kg, twice a day) injection. RESULTS: The inhibition percentage of the GPIAS test was significantly reduced post-salicylate injection in the tVNS and AS alone groups, while it was not significant in the tVNS with AS group. There was no significant difference in the mean percentage of the GPIAS test between the tVNS groups (with or without AS) after salicylate injections. Social interactions were significantly different in the AS alone group pre- and post-salicylate injections, but they were not significant in other groups. Moreover, the results of aggressive behavior tests showed significantly increased post-salicylate injections in the AS alone group, while they were not significant in the tVNS groups (with or without AS). CONCLUSIONS: The current study revealed that the application of tVNS alone produced improved social interaction and mood and alleviated salicylate-induced tinnitus severity. Moreover, combining tVNS with acoustic stimulation can prevent salicylate-induced tinnitus.

Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus-induced rats.

Objective: Despite 6%-20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus-induced rats. Methods: To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na-Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single-unit recordings were performed on a separate group that was treated as in group 4. Gap-prepulse inhibition of the acoustic startle (GPIAS) and pre-pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days. Results: Western blot analysis showed that the expression of γ-Aminobutyric acid Aα1 subunit (GABA Aα1), N-methyl-d-aspartate receptor subtype 2B (NR2B or NMDAR2B), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR1 (GluR1), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na-Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus. Conclusion: NPPC can play an effective role in the treatment of tinnitus in salicylate-induced rats, and MGB is one of the brain areas involved in these processes. Level of Evidence: NA.

Biosensors, Recent Advances in Determination of BDNF and NfL.

Key biomarkers such as Brain Derived Neurotrophic Factor (BDNF) and Neurofilament light chain (NfL) play important roles in the development and progression of many neurological diseases, including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. In these clinical conditions, the underlying biomarker processes are markedly heterogeneous. In this context, robust biomarker discovery is of critical importance for screening, early detection, and monitoring of neurological diseases. The difficulty of directly identifying biochemical processes in the central nervous system (CNS) is challenging. In recent years, biomarkers of CNS inflammatory response have been identified in various body fluids such as blood, cerebrospinal fluid, and tears. Furthermore, biotechnology and nanotechnology have facilitated the development of biosensor platforms capable of real-time detection of multiple biomarkers in clinically relevant samples. Biosensing technology is approaching maturity and will be deployed in communities, at which point screening programs and personalized medicine will become a reality. In this multidisciplinary review, our goal is to highlight clinical and current technological advances in the development of multiplex-based solutions for effective diagnosis and monitoring of neuroinflammatory and neurodegenerative diseases. The trend in the detection if BDNF and NfL.

Prevalence of depression, anxiety, and psychological distress in patients with epilepsy during COVID-19: A systematic review.

OBJECTIVE: COVID-19 pandemic disease has profound consequences for physical and mental health. In this regard, health care for chronic diseases, especially epilepsy is neglected The purpose of this systematic review study was to investigate the epidemic effect of COVID-19 on increasing the prevalence of mental disorders such as depression, anxiety, and sleep disorders in people with epilepsy (PWE). METHODS: We systematically searched MEDLINE, Cochrane, Embase, Web of science, Scopus, and Psych info databases for studies that estimate the prevalence of mental disorders in PWE during the COVID-19 until December 2020. Inclusion criteria included samples of population, with a confirmed diagnosis of epilepsy. RESULTS: Irrespective of PWE or people without epilepsy (PWOE), all experienced stress and anxiety during COVID-19 pandemic. Most of the studies showed that PWE and even PWOE during the pandemic, suffer from depression. The highest rate of depression was attributed to female PWE with financial problems (66.7%) and the lowest rate of depression in PWE was reported in 8.6%. 7.1-71.2% and 28.2% of patients reported sleep disorders and insomnia, respectively. Less than 2% experienced a sleep improvement. LIMITATIONS: Due to a large amount of heterogeneities across the results, we could not evaluate the exact rate of prevalence in spite of using effective measures. CONCLUSIONS: People with epilepsy were considered as a susceptible group to the impact of the pandemic. Therefore, great attention should be paid to PWE and adequate psychological supports provided in this period to relieve or inhibit risks to mental health in PWE.

The role of CA3 GABAB receptors on anxiolytic-like behaviors and avoidance memory deficit induced by D-AP5 with respect to Ca2+ ions.

Glutamatergic and GABAergic systems play key roles in the hippocampus and affect the pathogenesis of anxiety- and memory-related processes. Some investigations have assessed the role of balancing the function of these two systems in different areas of the central nervous system (CNS) as an approach to manage the related disorders. We investigated the anxiety and avoidance memory states using the test-retest protocol in the elevated plus maze to understand the role of GABAB receptors (GABABRs) in relation to the NMDA receptor blockade by D-AP5 (an NMDA receptor antagonist). Also, we examined the function of Ca2+ ions by blocking its entrance to the cell using SKF96365 (a Ca2+ channel blocker). The drugs were injected into the CA3 region before the test. Our data showed that D-AP5 induced anxiolytic-like behaviors and impaired the avoidance memory. Injection of baclofen (a GABABR agonist), but not phaclofen (a GABABR antagonist) induced anxiolytic-like behaviors. Neither baclofen nor phaclofen altered avoidance memory-related behaviors. When baclofen was injected before D-AP5, it potentiated the anxiolytic-like behaviors induced by D-AP5, but counteracted its effect on avoidance memory. Phaclofen pretreatment attenuated D-AP5-induced anxiolytic-like behaviors, but potentiated its effect on avoidance memory. The effect of baclofen application before D-AP5 on anxiety and phaclofen application before D-AP5 on avoidance memory at the heist doses were accompanied by a decrease in locomotion. The application of SKF96365 did not alter anxiety-like behaviors but induced avoidance memory impairment. SKF96365 application before the combination of baclofen and D-AP5 counteracted the effects produced by the combination of baclofen and D-AP5 on anxiety and memory states. Our findings showed that the CA3 GABABRs had a critical role in anxiolytic-like behaviors and avoidance memory deficit induced by D-AP5 and confirmed the role of Ca2+ ions in the observed results.

Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning.

Behavioral studies have suggested a key role for the cannabinoid system in the modulation of conditioned fear memory. Likewise, much of the literature has revealed that the serotonergic system affects Pavlovian fear conditioning and extinction. A high level of functional overlap between the serotonin and cannabinoid systems has also been reported. To clarify the interaction between the hippocampal serotonin (5-HT4) receptor and the cannabinoid CB1 receptor in the acquisition of fear memory, the effects of 5-HT4 agents, arachidonylcyclopropylamide (ACPA; CB1 receptor agonist), and the combined use of these drugs on fear learning were studied in a fear conditioning task in adult male NMRI mice. Pre-training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing time in both context- and tone-dependent fear conditions, suggesting impairment of the acquisition of fear memory. Pre-training, intra-hippocampal (CA1) microinjection of RS67333, a 5-HT4 receptor agonist, at doses of 0.1 and 0.2 or 0.2 µg/mouse impaired contextual and tone fear memory, respectively. A subthreshold dose of RS67333 (0.005 µg/mouse) did not alter the ACPA response in either condition. Moreover, intra-CA1 microinjection of RS23597 as a 5-HT4 receptor antagonist did not alter context-dependent fear memory acquisition, but it did impair tone-dependent fear memory acquisition. However, a subthreshold dose of the RS23597 (0.01 µg/mouse) potentiated ACPA-induced fear memory impairment in both conditions. Therefore, we suggest that the blockade of hippocampal 5-HT4 serotonergic system modulates cannabinoid signaling induced by the activation of CB1 receptors in conditioned fear.