Role of the caudate-putamen nucleus in sensory gating in induced tinnitus in rats.

Tinnitus can be described as the conscious perception of sound without external stimulation, and it is often accompanied by anxiety, depression, and insomnia. Current clinical treatments for tinnitus are ineffective. Although recent studies have indicated that the caudate-putamen nucleus may be a sensory gating area involved in noise elimination in tinnitus, the underlying mechanisms of this disorder are yet to be determined. To investigate the potential role of the caudate-putamen nucleus in experimentally induced tinnitus, we created a rat model of tinnitus induced by intraperitoneal administration of 350 mg/kg sodium salicylate. Our results revealed that the mean spontaneous firing rate of the caudate-putamen nucleus was increased by sodium salicylate treatment, while dopamine levels were decreased. In addition, electrical stimulation of the caudate-putamen nucleus markedly reduced the spontaneous firing rate of neurons in the primary auditory cortex. These findings suggest that the caudate-putamen nucleus plays a sensory gating role in sodium salicylate-induced tinnitus. This study was approved by the Institutional Animal Care and Use Committee of Peking University Health Science Center (approval No. A2010031) on December 6, 2017.

[Curative Efficacy of Rituximab for ITP Patients with Different Sensitivity to Hormone].

OBJECTIVE: To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant. METHODS: Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively. RESULTS: The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P＜0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients. CONCLUSION: The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.

[Effect of Lentiviral Vector-Mediated CXCR4 Gene Overexpression on Mesenchymal Stem Cell Homing Capacity].

OBJECTIVE: To explore the effects of lentiviral-mediated CXC chemokine receptor-4（CXCR-4）gene over-expression on the homing capacity of mesenchymal stem cells（MSC）in vivo. METHODS: The MSC overexpressing CXCR-4 were constructed by using the lentiviral vector-mediated mouse MSC overexpressing the CXCR-4 gene. The BALB/c mice were divided into 3 group: simple radiation group（TBI）in which mice exposed to total body irradiation, then were infused with normal saline; EGFP-MSC group in which mice were infused with MSC（5×105）transducted by EGFP via tail vein after TBI; and CXCR-4-MSC group in which mice were infused with MSC (5×105) simultaneously carraying EGFP and CXCR-4 gene via tail vein after TBI. The mice were sacrified at 24 hours after infusion, the frozen sections were prepared to detect the distribution of infused MSC. Furthermore, the numbers of MSC homing into spleen and bone marrow was detected by flow cytometry, and the level of stromal cell-derived factor-1(SDF-1) was detected by ELISA. RESULTS: The frozen section showed that the CXCR-4 over-expression could significantly enhance the efficacy of MSC homing into lung, liver and spleen; the flow cytonetry detection slowed that the number of over-expressed CXCR-4 MSC homing into spleen and bone matrow was sigmificantly higher than that in EGFP-MSC group（P<0.05）, the ELISA showed that the SDF-1 level in peripheral blood and bone marrow after 24 hours of irradiation significantly incrtaoed （P<0.05）, moreover, the SDF-1 level increase was associcted with horming efficacy of MSC with CXCR-4 overexpression. CONCLUSION: overexpression CXCR-4 gene mediated by lentiviral vector can prmote the efficacy of MSC homing into spleen and bone marrow.

Effect of Neuronal Excitability in Hippocampal CA1 Area on Auditory Pathway in a Rat Model of Tinnitus.

BACKGROUND: Tinnitus is a common disorder that causes significant morbidity; however, the neurophysiological mechanism is not yet fully understood. A relationship between tinnitus and limbic system has been reported. As a significant component of the limbic system, the hippocampus plays an important role in various pathological processes, such as emotional disturbance, decreased learning ability, and deterioration of memory. This study was aimed to explore the role of the hippocampus in the generation of tinnitus by electrophysiological technology. METHODS: A tinnitus model was established in rats through intraperitoneal injection of salicylate (SA). Subsequently, the spontaneous firing rate (SFR) of neurons in the hippocampal CA1 area was recorded with in vivo multichannel recording technology to assess changes in excitability induced by SA. To investigate the effect of excitability changes of hippocampus on the auditory pathway, the hippocampus was electrically stimulated and neural excitability in the auditory cortex (AC) was monitored. RESULTS: Totally 65 neurons in the hippocampal CA1 area were recorded, 45 from the SA group (n = 5), and 20 from the saline group (n = 5). Two hours after treatment, mean SFR of neurons in the hippocampal CA1 area had significantly increased from 3.06 ± 0.36 Hz to 9.18 ± 1.30 Hz in the SA group (t = -4.521, P < 0.05), while no significant difference was observed in the saline group (2.66 ± 0.36 Hz vs. 2.16 ± 0.36 Hz, t = 0.902, P > 0.05). In the AC, 79.3% (157/198) of recorded neurons showed responses to electrical stimulation of the hippocampal CA1 area. Presumed pyramidal neurons were excited, while intermediate neurons were inhibited after electrical stimulation of the hippocampus. CONCLUSIONS: The study shows that the hippocampus is excited in SA-induced tinnitus, and stimulation of hippocampus could modulate neuronal excitability of the AC. The hippocampus is involved in tinnitus and may also have a regulatory effect on the neural center.

[Research Progress on Effect of JAK Inhibitors on Myelofibrosis- Review].

Myelofibrosis(MF) is a type of myeloprolifirative neoplasms which is difficult to be treated. With the discovery of V617F mutation site in Janus kinase 2 (JAK2), JAK inhibitor provides a new treatment strategy for patients with myelofibrosis. Since 2011 the FDA in USA approved the first generation of JAK inhibitor Ruxolitinib for marketing, a growing number of JAK inhibitors have been entering into the clinical trials and showed a certain clinical efficacy. On the one hand, some JAK inhibitors for single application can effectively relieve the clinical symptoms of patients with myelofibrosis, slow down disease progression, and prolong the survival; on the other hand, JAK inhibitor can also be applied in combination with traditional or other new targeted drugs for MF patients, even during the allogenetic hematopoietic stem cell transplantation, thus providing more choices for targeted therapy on the patients with myelofibrosis. This review focuses mainly on the latest advances of JAK inhibitors for the patients with myelofibrosis.

Body mass index trajectories during infancy and pediatric obesity at 6 years.

PURPOSE: The purpose of the article was to examine the relationship between body mass index (BMI) trajectories during infancy and risk of obesity at the age of 6 years. METHODS: We used data on 1169 children with at least two BMI measures during their first year of life from the Infant Feeding Practices Survey II and its Year 6 Follow-Up. Latent class growth analysis was used to identify distinct trajectories of BMI, and multiple logistic regression analyses were used to assess the association of the identified trajectories with obesity at the age of 6 years. RESULTS: Three trajectories of BMI were identified during the first year of life: low stable (80.2%), high stable (16.9%), and rising (2.8%). Obesity at the age of 6 years was highest among children with a high-stable trajectory (17.2%), followed by the low-stable (9.6%) and rising (9.1%) groups. Compared with those in the low-stable trajectory, the adjusted odds ratio for obesity at the age of 6 years was 1.79 (95% confidence interval 1.13-2.84) in children with the high-stable growth trajectory and 0.84 (0.26-2.72) in children with the rising growth trajectory. CONCLUSIONS: High-stable BMI trajectory in infancy resulted in a higher risk for obesity at the age of 6 years, but had low accuracy for identifying obese children at the age of 6 years.

MicroRNA-92 expression may be associated with reduced estrogen receptor ß1 mRNA levels in cervical portion of uterosacral ligaments in women with pelvic organ prolapse.

OBJECTIVE: This study examined microRNA-92 (miR-92) expression level in relation to the mRNA level of its potential target gene, estrogen receptor ß1 (ERß1), in female patients diagnosed with pelvic organ prolapse (POP). STUDY DESIGN: Between July 2012 and September 2014, a total of 104 patients were recruited at the First Affiliated Hospital of Sun Yat-sen University, which included 56 POP patients and 48 non-POP control subjects. Based on POP-Q score, the POP patients were further categorized into POP II and POP III groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify miR-92 expression level. ERß1 tissue expression was measured by western blot and immunohistochemistry (IHC) methods. SPSS 19.0 software was used for statistical analysis. RESULTS: No remarkable differences were observed between the POP group and non-POP group, and between the POP II and POP III groups, with respect to age, body mass index (BMI), parity, menopause status, and family history of POP. The expression level of miR-92 in the POP group was dramatically higher than the non-POP group (P<0.05). Consistent with the disease status, miR-92 expression level in POP III group was markedly higher than the POP II group (P<0.05). Western blot analysis revealed significantly reduced levels of ERß1 in the POP group compared to the non-POP group, with similar results obtained between the POP III and POP II groups (all P<0.05). IHC results showed ERß1 staining mainly in the nucleus and semi-quantitative measurements, expressed as positive expression rate, revealed that ERß1 level in the POP group was clearly lower than non-POP group. Finally, statistical analysis of IHC results from uterosacral ligament tissue showed inverse correlation between miR-92 and ERß1 expression levels in POP patients (P<0.05). CONCLUSIONS: Our results revealed increased miR-92 expression and decreased ERß1 level in uterosacral ligaments of women diagnosed with POP, compared to non-POP subjects POP III patients exhibited more severe changes than POP II patients. Further, ERß1expression is inversely correlated to miR-92 expression. Taken together, our results suggest that miR-92 and ERß1 expression levels may be used as reliable diagnostic markers for assessing the severity of POP.

Effects of tetrathiomolybdate and penicillamine on brain hydroxyl radical and free copper levels: a microdialysis study in vivo.

Wilson disease is an inherited disorder of excessive copper accumulation. The commonly used drug d-penicillamine (PA) or trientine both cause a high incidence (10-50%) of neurological worsening, which rarely occurs with tetrathiomolybdate (TM) treatment. To investigate the mechanisms of neurologic deterioration after the initiation of chelation therapy, brain hydroxyl radical and free copper were assessed in vivo in this study. On days 3, 7, 14, and 21 after PA or TM administration, striatal hydroxyl radical levels of both TX mice and controls were assessed by terephthalic acid (TA) combined with microdialysis and high-performance liquid chromatography (HPLC). Within the same microdialysis samples, free copper was measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that both hydroxyl radical and free copper markedly increased in the striatum of TX mice during PA administration but were not elevated when administering TM. These results suggested that the further increased free copper in the brain and oxidative stress caused by some chelators might contribute to the neurological deterioration.

Absorption properties and mechanism of trolline and veratric acid and their implication to an evaluation of the effective components of the flowers of Trollius chinensis.

AIM: To study the absorption properties and mechanism of two important components, trolline and veratric acid, from the flowers of Trollius chinensis, in order to better understand the contribution of these two compounds to the effectiveness of these flowers. METHOD: The human Caco-2 cell monolayer model was employed to study the transport of trolline and veratric acid from apical side (AP) to basal side (BL), and from BL to AP by determining the transport rates as the function of time and concentration and calculating apparent permeability coefficients (Papp). RESULTS: Trolline and veratric acid were transported across Caco-2 cell monolayer through different mechanisms in a concentration dependent manner. Trolline was transported at a Papp level of 10(-6) cm·s(-1) with a Papp AP→BL/Papp BL→AP ratio of more than 1.8 or less than 0.8, while veratric acid was transported at a Papp level of 10(-5)cm·s(-1) with a Papp AP→BL/Papp BL→AP ratio of close to 1.0. CONCLUSION: Trolline is moderately absorbed through an associative mechanism involving active and passive transport, and veratric acid is well-absorbed mainly through passive diffusion. These factors should be taken into account when chemically assessing the pharmacodynamic material basis of the flowers of T. chinensis.

Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro.

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.

Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells.

Aß40-induced vascular dysfunction has been implicated in the pathogenesis of Alzheimer׳s disease (AD). In the present study, we investigated the possible protective effects of puerarin against Aß40-induced vascular damage and impairment to angiogenesis in transgenic TG (fli1:EGFP) zebrafish and human endothelial cells. Aß40 peptides at 5µM caused an obvious reduction of vessel branches in the subintestinal vein basket, induced NADPH oxidase-derived reactive oxygen species and impaired vascular endothelial growth factor (VEGF)-dependent angiogenesis. Pretreatment with puerarin attenuated Aß40-induced vessel reduction and impairment to angiogenesis in a dose-dependent manner. In addition, Aß40 decreased VEGF-dependent phosphorylation of Akt and eNOS, whereas puerarin treatment attenuated these detrimental effects. Furthermore, the restoration of Aß40-induced-angiogenesis impairment by puerarin was abolished by either the PI3 kinase inhibitor LY294002 (10µM) or eNOS inhibitor L-NAME. The present study suggests that puerarin exerts its protective action probably through reduction of NADPH oxidase-derived reactive oxygen species overproduction and activation of the PI3K/Akt/eNOS pathways.

A 65-year-old man with infratentorial diffuse encephalopathy and hydrocephalus.

Tuberculous encephalopathy (TBE) is an important diagnosis in countries with a high prevalence of tuberculosis. TBE is a life-threatening condition but rarely reported in the modern literature. We reported a case of a man with extensive parenchymal lesions involving the brainstem and right cerebellar hemisphere that resolved after treatment. The clinical, laboratory and pathological features of this case are highlighted and the pathogenesis is discussed.

Anti-tuberculosis treatment for Devic's neuromyelitis optica.

There are no specific treatments for patients with acute, severe neurological deficits caused by neuromyelitis optica (NMO) who fail to recover after treatment with high-dose corticosteroids. We evaluated the clinical response of anti-tuberculosis treatment (ATT) in patients suffering from steroid-refractory NMO, and investigated the correlation between NMO and tuberculous infection of the central nervous system (CNS). We conducted this prospective, controlled study in southern China. Twelve patients with steroid-refractory NMO were monitored during ATT and compared with a control group of 13 patients with the same type of NMO who received current standard therapies. A molecular diagnostic test was carried out and Extended Disability Status Scale (EDSS) score analysis, visual acuity, the number of relapses and MRI changes were evaluated at study entry and after 1 and 2years of therapy. ATT may lead to the recovery of important neurological functions and all our patients responded positively to therapy. EDSS score and visual acuity improved and abnormalities in the spinal cord, observed by MRI, markedly decreased over time. ATT also significantly reduced the rate of relapse. By comparison, in the control group, a significant clinical deterioration was observed, and patients did not show favourable EDSS scores and MRI changes. This study suggests that CNS infection with Mycobacterium tuberculosis is an important cause of NMO.

[Expression of MIF, VEGF and p16 proteins and their correlation with clinicopathological features in cervical cancer].

OBJECTIVE: To investigate the expression of macrophage migration inhibitory factor (MIF), p16 and vascular endothclial growth factor (VEGF) proteins and their relationship with clinicopathological features in cervical cancer. METHODS: Tissue microarray (TMA) and immunohistochemistry were used to detect the expression of MIF, p16 and VEGF proteins in specimens of 10 normal cervical epithelial tissues, 18 cervical intraepithelial neoplasia (CIN II, III) and 31 cervical squamous cell carcinomas. Western blotting was used to detect the expression of MIF, p16 and VEGF proteins in fresh samples of 3 normal cervical epithelial tissues, 3 CIN (III) and 6 cervical squamous cell carcinomas (3 Ib and 3 IIb). RESULTS: Positive expression rates of MIF were 0, 72.2% and 93.5% in the normal, CIN and carcinoma samples, 20.0%, 33.3% and 71.0% for p16, and 10.0%, 44.4% and 74.2% for VEGF, respectively. The expression rates and levels of the three genes were significantly higher in cervical carcinomas than those in CIN. MIF expression was significantly higher in the cases with lower differentiation (17 cases, P = 0.021), and was positively correlated with VEGF expression (P = 0.0045). VEGF expression rate was significantly higher in both cases of poorly differentiated carcinomas and those with stage II b carcinoma or beyond (P = 0.004, P = 0.008). p16 expression was not found to be correlated with tumor differentiation or clinical stage. It was showed by Western blotting that the expression levels of MIF, VEGF and p16 were significantly higher in the carcinomas than those in CIN or normal tissues. CONCLUSION: Expression of MIF, VEGF and p16 are probably involved in the process of cervical carcinogenesis. MIF expression is correlated with tumor differentiation. VEGF expression is correlated with both tumor differentiation and clinical stage.

Change of extracellular ascorbic acid in the brain cortex following ice water vestibular stimulation: an on-line electrochemical detection coupled with in vivo microdialysis sampling.

BACKGROUND: Ascorbic acid (AA) represents one of the most important enzyme co-factors, antioxidants and neuromodulators and plays an important role in the cerebral system. Increasing evidence has suggested that AA could treat certain kinds of vertigo diseases such as Meniere's disease. To elucidate the neurochemical functions associated with AA in vertigo, the change of extracellular AA in the brain cortex following caloric vestibular stimulation (CVS) was evaluated. METHODS: An on-line electrochemical detection was coupled with in vivo microdialysis to continuously monitor the change of extracellular AA in the primary somatosensory (SI) area of guinea pigs following a caloric vestibular stimulation. Sixteen guinea pigs were divided into three groups, i.e., experimental group with irrigation of the ear canal with ice water (0 degrees C) (n = 8), and two control groups, one with irrigation of the ear canal with warm water (38 degrees C) (n = 4) and the other with irrigation of the auricle with ice water (n = 4). RESULTS: In the experimental group, the ice water irrigation of the left external ear canal induced a horizontal nystagmus towards the right side lasting about 45 seconds. No nystagmus was induced by warm water irrigation of the external ear canal or by ice water irrigation of the auricle. The extracellular AA concentration significantly increased following the ice water vestibular stimulation, reaching a maximum of (130 +/- 20)% (n = 8) of the basal dialysate level (2.61 +/- 0.92) micromol/L (n = 8), lasting at least for an hour. AA level did not change distinctly after the irrigation of the left external ear canal with warm water or the irrigation of the auricle with ice water. CONCLUSIONS: The concentration of extracellular AA in the brain cortex of the SI area increased following the ice water vestibular stimulation. This demonstration may be useful for the investigation of the neurochemical processes associated with AA in the process of vertigo.

Effects of caloric vestibular stimulation on serotoninergic system in the media vestibular nuclei of guinea pigs.

BACKGROUND: Anatomic and electrophysiological studies have revealed that the neurons located in the media vestibular nuclei (MVN) receive most of the sensory vestibular input coming from the ipsilateral labyrinth and the responses of MVN neurons to caloric stimulation directly reflect changes in primary vestibular afferent activity. The aim of this study was to clarify the intrinsic characteristics of serotonin (5-hydroxytryptamine, 5-HT) release in the MVN during the period of vertigo induced by caloric stimulation. METHODS: We used an in vivo microdialysis technique to examine the effects of caloric stimulation on the serotoninergic system in MVN. Twenty four guinea pigs were randomly divided into the groups of irrigation of the ear canal with hot water (n = 6), ice water (n = 6) and 37 degrees C water (n = 4), and the groups of irrigation of the auricle with hot water (n = 4) and ice water (n = 4), according to different caloric vestibular stimulation. We examined the animal's caloric nystagmus with a two-channel electronystagmographic recorder (ENG), and meanwhile examine serotonin (5-hydroxytryptamine, 5-HT) level in the MVN with microdialysis technique after caloric stimulation. RESULTS: In the caloric test the hot water (44 degrees C) irrigation of the right external auditory canal induced horizontal nystagmus towards the right side lasting about 60 seconds and the ice water irrigation of the right external auditory canal induced it towards the left side lasting for about 90 seconds. No nystagmus was induced by 37 degrees C water irrigation of the external ear canal. Therefore, it was used as a negative control stimulation to the middle ear. The MVN 5-HT levels significantly increased in the first 5-minute collecting interval and increased to 254% and 189% of the control group in the second collecting interval in response to caloric vestibular stimulation with ice water and hot water respectively. The serotonin release was not distinctly changed by the irrigation of the auricle with ice water or hot water. CONCLUSIONS: Neither somato-sensory stimulation of the middle ear nor nonspecific cold or hot stress affects the serotonin release. The rise of 5-HT in MVN may be involved in the mechanism of vertigo induced by caloric stimulation.

[Inhibition of salicylate on potassium channels in rat inferior colliculus neurons].

OBJECTIVE: To understand what role of the transient outward potassium channels and the delayed rectifier potassium channels play in the mechanism of salicylate-induced tinnitus. METHODS: The effects of salicylate on the transient outward potassium channels and the delayed rectifier potassium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method. RESULTS: Salicylate blocked the transient outward potassium current (I(K(A and the delayed rectifier potassium current (I(K(DR in concentration-dependent manner (0.1-1 mmol/L). The IC50 values for the blocking action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mmol/L, respectively. At a concentration of 1 mmol/L, salicylate did not shift the activation and inactivation curves of I(K(A)), but significantly shifted the activation and inactivation curves of I(K(DR)) negatively by approximately 11 mV and 24 mV. CONCLUSIONS: Salicylate inhibits both I(K(A)) and I(K(DR)) in rat inferior colliculus neurons but only significantly affects the activation and inactivation kinetics of I(K(DR)). Effects of I(K(A)) and I(K(DR)), especially I(K(DR)), by salicylate may play an important role in salicylate-induced tinnitus.

[Study of neurological mechanism of lidocaine's suppression to tinnitus via microdialysis].

OBJECTIVE: To elucidate the neurological mechanism of lidocaine's suppression to tinnitus. METHODS: Thirty-four Wistar rats weighing 300-350 grams were randomly divided into IC group (n = 17) and AC group (n = 17), according to microdialysis region. Each group was randomly subdivided into saline treatment group (n = 4), salicylate treatment group (n = 6), and salicylate + lidocaine treatment group (n = 7). Using in vivo microdialysis technique coupled with microbore HPLC-electrochemical detection, the present study first monitored the 5-HT release in IC and AC in salicylate-induced tinnitus animal models, and then, examined the effects of lidocaine on salicylate-induced 5-HT changes in IC and AC. The statistical analysis was performed using two-way ANOVA for repeated measures of raw data with time and treatment condition as main effects. Individual time-point values between no more than two groups were compared with the unpaired Student's t-test. The accepted level of significance was 0.05, two-tailed. RESULTS: The 5-HT level increased to a maximum of 268% +/- 27% (mean +/- s) basal level in IC 2 h after salicylate application and of 277% +/- 24% basal level in AC around 3 h after application. And then, the 5-HT level gradually decreased to 157% +/- 16% of baseline in IC and 180% +/- 18% of baseline in AC by the end of the sixth hour. Saline did not alter the IC and AC dialysate 5-HT level in control rats. Two-way ANOVA with repeated measures indicated a significant effect of the condition factor [F (1, 8) = 413.949, P < 0.000001 in IC group; F(1,8) = 192.184, P < 0.000001 in AC group]. The increases of 5-HT levels in salicylate treatment groups were significantly reduced to 85% +/- 8% basal level in IC and 92% +/- 26% basal level in AC after local infusion of 1% lidocaine (P < 0.05). Compared with corresponding control value at that time (unpaired student t-test). Two-way ANOVA with repeated measures showed a significant difference between the salicylate group and salicylate + lidocaine group [P < 0.000001 with F(1, 11) = 329.267 for the condition factor in IC subgroup; P < 0.000001 with F(1, 11) = 133.844 for the condition factor in AC subgroup]. CONCLUSION: The suppression of lidocaine to tinnitus may be associated with the decrease of 5-HT level in IC and AC.