Our results may indicate that vestibular symptoms in pediatric patients may act as a predisposing factor to develop vestibular migraine at an earlier age in adulthood.

Background: Ectodomain shedding by the metalloproteinase family affects axon guidance and neurite outgrowth. Results: IgLON family members are metalloproteinase substrates that promote neurite outgrowth in a metalloproteinase-dependent manner. Conclusion: IgON family members are shed from the surface of cortical neurons to promote neurite extension. Significance: Proteolytic cleavage of IgLON family members could have critical roles in specific targeting and synaptogenesis in cortical neurons.

Background and purpose: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague-Dawley (SD) rats after an injection of CDDP (5 mgkg -1 body weight). Experimental approach: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic-related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed. Key results: CDDP significantly increased the levels of caspase-3/7 activity and active caspase-3 protein expression and caspase-3 immunofluorescence staining, caspase-9 activity, and Bax protein expression but decreased Bcl-2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment. Conclusions and implications: These findings support the hypothesis that cisplatin-related apoptosis evokes an intrinsic pathway of pro-apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin-induced ototoxicity.

Damaged central nervous system (CNS) neurons have a poor ability to spontaneously regenerate, causing persistent functional deficits after injury. Therapies that stimulate axon growth are needed to repair CNS damage. 14-3-3 adaptors are hub proteins that are attractive targets to manipulate cell signaling. We identify a positive role for 14-3-3s in axon growth and uncover a developmental regulation of the phosphorylation and function of 14-3-3s. We show that fusicoccin-A (FC-A), a small-molecule stabilizer of 14-3-3 protein-protein interactions, stimulates axon growth in vitro and regeneration in vivo. We show that FC-A stabilizes a complex between 14-3-3 and the stress response regulator GCN1, inducing GCN1 turnover and neurite outgrowth. These findings show that 14-3-3 adaptor protein complexes are druggable targets and identify a new class of small molecules that may be further optimized for the repair of CNS damage.

Toll-like receptors trigger the innate immune response by activating various cell types such us macrophages and lymphocytes. We genotyped SNV of TLR3, TRL7, TLR8 and TLR10 in 863 Spanish and 150 Italian patients with Meniere's disease (MD) and 1,013 controls by using Taqman assays. Real-Time qPCR was used to measure the expression level of TLR10 in peripheral blood leukocytes. The overall dataset showed that the C allele and the CC genotype of rs11096955 in TLR10 gene were more commonly observed in controls than patients (corrected p = 1 × 10(-3), OR = 0.68 [95 % confidence interval, 0.54-0.84] for CC genotype; corrected p = 1.5 × 10(-5), OR = 0.75 [0.66-0.85] for allele C). Moreover, the CC genotype was more frequent in patients with uni- (19 %) than bilateral sensorineural hearing loss (SNHL) (13 %). Logistic regression demonstrated that the time since the onset of MD, Tumarkin crises, hearing stage and rs11096955 were independent factors influencing the risk of bilateral SNHL. In addition, rs11096955 influenced hearing loss progression in patients with bilateral MD. No change in expression of TLR10 was observed according to CC, CA or AA genotypes. Our data suggest that allelic variants of TLR10 gene may influence the susceptibility and time-course of hearing loss of MD in the European population.

Patients: Five hundred ten individuals from 8 hospitals that met the American Academy of Otolaryngology-Head and Neck Surgery diagnostic criteria for definitive Ménière's disease. Intervention: Conservative treatment. Main Outcome Measure: Frequency and duration of episodes of definitive vertigo during follow-up. Results: Ménière's disease affects both sexes and both ears equally, with onset generally in the fourth decade

Migraine is a common neurological disorder characterized by episodic headaches with specific features, presenting familial aggregation. Migraine is associated with episodic vertigo, named Vestibular Migraine (VM) whose diagnosis mainly rely on clinical history showing a temporary association of symptoms. Some patient refers symptoms occurring in pediatric age, defined “episodic symptoms which may be associated with migraine.” The aim of this cross sectional observational study was to assess migraine-related clinical features in VM subjects. For the purpose, 279 patients were recruited in different centers in Europe; data were collected by a senior neurologist or ENT specialist through a structured questionnaire. The age of onset of migraine was 21.8 ± 9. The duration of headaches was lower than 24 h in 79.1% of cases. Symptoms accompanying migrainous headaches were, in order of frequency, nausea (79.9%), phonophobia (54.5%), photophobia (53.8%), vomiting (29%), lightheadedness (21.1%). Visual or other auras were reported by 25.4% of subjects. A familial aggregation was referred by 67.4%, while migraine precursors were reported by 52.3% of subjects. Patients reporting nausea and vomiting during headaches more frequently experienced the same symptoms during vertigo. Comparing our results in VM subjects with previously published papers in migraine sufferers, our patients presented a lower duration of headaches and a higher rate of familial aggregation; moreover some common characters were observed in headache and vertigo attacks for accompanying symptoms like nausea and vomiting and clustering of attacks.

Caspase-3/7 activity, as well as caspase-3 gene expression, were statistically higher in early-mature rats (EM, 276,139+/-13 669 RLUs (relative light units), p<0.001; and 390+/-50 arbitrary units, p=0.0017, respectively) or in aged-mature rats (AM, 371,020+/-26,457, p<0.0001; and 1510+/-90, p<0.0001, respectively) than younger rats (YR 147,129+/-8485 and 0.14+/-0.004, respectively). An increased caspase-9 activity with ageing was also observed (YR 49,932+/-2046 RLUs vs EM 260,890+/-5939, p<0.0001 or AM 118,241+/-12,423, p<0.0001). Caspase-8 activity was not affected significantly by age. Bax protein expression also increased by age (YR 38,200+/-1790 arbitrary units vs EM 76,549+/-5450, p<0.05), in contrast to Bcl-xL protein expression (YR 27,000+/-5000 arbitrary units vs EM 10,200+/-5000, p<0.005).