Kainic acid (KA)-induced seizures followed by neuronal death are associated with neuroinflammation and blood-brain barrier (BBB) leakage. Tonicity-responsive enhancer binding protein (TonEBP) is known as a transcriptional factor activating osmoprotective genes, and in brain, it is expressed in neuronal nuclei. Thus dysregulation of TonEBP may be involved in the pathology of KA-induced seizures. Here we used TonEBP heterozygote ( þ / À ) mice to study the roles of TonEBP. Electroencephalographic study showed that TonEBP ( þ / À ) mice reduced seizure frequency and severity compared with wild type during KA-induced status epilepticus. Immunohistochemistry and western blotting analysis showed that KA-induced neuroinflammation and BBB leakage were dramatically reduced in TonEBP ( þ / À ) mice. Similarly, TonEBP-specific siRNA reduced glutamate-induced death in HT22 hippocampal neuronal cells. TonEBP haplodeficiency prevented KA-induced nuclear translocation of NF-jB p65 and attenuated inflammation. Our findings identify TonEBP as a critical regulator of neuroinflammation and BBB leakage in KA-induced seizures, which suggests TonEBP as a good therapeutic target.
Rationale : Many clinical trials have been conducted with the aim at preventing Chronic obstructive pulmonary disease (COPD) and reducing symptoms, disability, and mortality. Recently, many studies have focused on combination therapy with inhaled corticosteroids (ICS), long−acting ß2−agonists (LABA), and long−acting anticholinergics. However, additional effects of such medications, if any, are unknown. We undertook this study to demonstrate adding tiotropium to previously used bronchodilators and ICS provides beneficial effects in patients with stable COPD. Methods : A retrospective analysis of patients with COPD treated at the Korea University Guro Hospital between March 1996 and June 2008 was conducted. Changes in pulmonary function test (PFT) results after use of tiotropium with existing medications were calculated and compared in COPD patients. Results : A total of 50 patients who underwent PFTs were included in this study. Use of tiotropium in COPD patients who had been receiving bronchodilators and/or ICS resulted in significant improvement of FEV1 (%) and reductions in TLC(%), RV(%), and FRC(%). These additional effects were more prominent in LABA plus ICS users and more severe COPD patient groups. Conclusions : We propose that adding tiotropium to existing therapy with other bronchodilators and/or ICS is effective for improving pulmonary function and air trapping in COPD patients. This abstract is funded by: None. Am J Respir Crit Care Med 179;2009:A4561 Internet address: www.atsjournals.org Online Abstracts Issue
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.