Background: Inefficient remyelination of demyelinated plaques in multiple sclerosis (MS) leads to secondary axon degeneration and progressive disability. Therapies that potentiate remyelination would be of immense help for managing MS. Objective: Here, we report the effects of valproic acid (VPA) on focal experimental autoimmune encephalomyelitis (fEAE). Methods: fEAE was induced in Wistar rats by immunizing the animals with guinea pig spinal cord homogenate emulsified in complete Freund's adjuvant and with pertussis toxin (PT) injection into the spinal cord at the level of T8 vertebra on day 18 after immunization. VPA 300 mg/kg was applied for 4 days after or 8 days before PT administration. Behavioral evaluation, histological assessment and immunohistofluorescence assays were used to evaluate the outcomes. Results: VPA administration had no effect on the development of symptoms, but after discontinuing VPA, animals showed faster recovery. Eight days of pretreatment with VPA accelerated the recovery phase of EAE and increased the number of remyelinated axons in the lesion area. VPA pretreatment also increased the recruitment of neural stem cells and oligodendrocyte precursors within the lesion. Conclusions: Results suggest VPA as a potential therapy for remyelinating the lesions in MS and for faster recovery from disease relapses. The effect of VPA seems to be mediated by endogenous progenitors recruitment.

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Asthma represents an episodic and fluctuating behavior characterized with decreased complexity of respiratory dynamics. Several evidence indicate that asthma severity or control is associated with alteration in variability of lung function. The pathophysiological basis of alteration in complexity of breathing pattern in asthma has remained poorly understood. Regarding the point that Rho-kinase is involved in pathophysiology of asthma, in present study we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in a guinea pig model of asthma. Male Dunkin Hartley guinea pigs were exposed to 12 series of inhalations with ovalbumin or saline. Animals were treated by the Rho-kinase inhibitor Y-27632 (1mM aerosols) prior to each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Complexity analysis of respiratory dynamics revealed a dramatic decrease in irregularity of respiratory rhythm representing less complexity in asthmatic guinea pigs. Inhibition of Rho-kinase reduced the airway remodeling and hyperreponsiveness, but had no significant effect on lung inflammation and complexity of respiratory dynamics in asthmatic animals. It seems that airway hyperresponsiveness and remodeling do not significantly affect the complexity of respiratory dynamics. Our results suggest that inflammation might be the probable cause of shift in the respiratory dynamics away from the normal fluctuation in asthma.

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Introduction:The incidence of diabetes is increasing along with its associated respiratory disorders, sleep disturbance and mental health problems. Despite the adverse effects of benzodiazepine receptor agonists (BZRAs) on the respiratory system function, they remain the most commonly used medications for the management of anxiety and sleep disorders. The aim of this study was to investigate whether chronic hyperglycemia increases the adverse respiratory effects of BZRAs. Methods:The experiments were carried out in male Wistar rats that were randomly allocated into six experimental groups. Hyperglycemia was induced by injecting 35mg/kg streptozotocin (STZ). We recorded breathing of conscious animals using whole-body plethysmography at the onset of the experiment and three weeks after diabetes induction. Animals were subjected to intraperitoneal injection of midazolam (0.75mg/kg) and diazepam (1mg/kg) 15min prior to the second respiratory recording.Results: Analysis of respiratory dynamics revealed an alteration in breathing pattern in intact animals following the anxiolytic dose of benzodiazepines, which was associated with an increase in respiration rate and variability and decrease in the irregularity of the respiratory rhythm. Meanwhile, these effects were significantly decreased in hyperglycemic animals. Conclusion:Our results demonstrate that STZ-induced hyperglycemic rats exhibited decreased adverse respiratory effects of BZRAs. It seems that hyperglycemia induced an impairment in benzodiazepine receptors response to the BZRAs.