en P77: NADPH Oxidase Type 4 Inhibits Immune Cell Trafficking into The Central Nervous System During Neuroinflammation تحقیقات پایه در علوم اعصاب Basic research in Neuroscience پژوهشي Research --- Open Access, CC-BY-NC &nbsp; <table border="0" cellpadding="5" cellspacing="2" dir="rtl" id="table_article" style="text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Tahoma; word-spacing: 0px; orphans: 2; widows: 2; break-inside: avoid !important; background-color: rgb(251, 250, 249); -webkit-text-stroke-width: 0px; text-decoration-style: initial; text-decoration-color: initial;" width="100%"> <tbody style="text-align: justify; line-height: 2.2; font-size: 12px; margin-top: 0px; margin-bottom: 0px; break-inside: avoid !important;"> <tr style="break-inside: avoid !important;"> <td class="abstractmed" colspan="2" style="text-align: justify; break-inside: avoid !important;"> <p style="text-align: center; font-size: 12px; margin-top: 0px; margin-bottom: 0px;"><span style="text-align: center; color: rgb(0, 0, 0); font-family: Tahoma; font-size: 12px; background-color: rgb(251, 250, 249);">لطفاً به چکیده انگلیسی مراجعه شود.</span></p> </td> </tr> <tr style="break-inside: avoid !important;"> </tr> </tbody> </table> <div style="text-align: justify;">Transendothelial trafficking of immune cells into the central nervous system (CNS) and disruption of the blood brain barrier (BBB) are pathophysiological hallmarks of neuroinflammatory disorders like multiple sclerosis (MS). Accumulating evidence suggest that oxidative stress plays a major role in the pathogenesis of MS, whereas a specific influence of oxidative stress on BBB dysfunction in MS was unclear so far. Here, we identify NADPH oxidase type 4 (NOX4) as a specific and direct modulator of BBB integrity. Deficiency of NOX4, but not NOX1 or NOX2, rendered mice more susceptible to experimental autoimmune encephalomyelitis (an animal model of MS) and was accompanied by a remarkable enhancement of BBB disruption and CNS inflammation. Murine and human in vitro analysis revealed that lack of NOX4 amplifies leukocyte trafficking by modified endothelial cells. Further, reduced endothelial NOX4 expression was found in CNS tissue of individuals suffering from MS indicating an important role of NOX4 also in humans. Our study demonstrates, for the first time, that NOX4 is an important and direct regulator of BBB integrity. NOX4 activation can decrease BBB damage and cell invasion during neuroinflammation and may offer a novel strategy for the treatment of MS.<br> &nbsp;</div> NADPH Oxidase, Immune Cells, Neuroinflammation 108 108 http://shefayekhatam.ir/browse.php?a_code=A-10-24-1247&slc_lang=en&sid=1 Alexander M Herrmann Alexander M Herrmann Alexander.Herrmann@ukmuenster.de 100319475328460016178 100319475328460016178 Yes Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Kerstin Göbel Kerstin Göbel 100319475328460016179 100319475328460016179 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Susann Eichler Susann Eichler 100319475328460016180 100319475328460016180 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Johanna Breuer Johanna Breuer 100319475328460016181 100319475328460016181 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Sarah Glumm Sarah Glumm 100319475328460016182 100319475328460016182 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Stjepana Kovac Stjepana Kovac 100319475328460016183 100319475328460016183 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Tobias Ruck Tobias Ruck 100319475328460016184 100319475328460016184 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Monika Merker Monika Merker 100319475328460016185 100319475328460016185 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Petra Hundehege Petra Hundehege 100319475328460016186 100319475328460016186 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Lisa Epping Lisa Epping 100319475328460016187 100319475328460016187 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Eva Geuss Eva Geuss 100319475328460016188 100319475328460016188 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Harald H. H. W. Schmidt Harald H. H. W. Schmidt 100319475328460016189 100319475328460016189 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Christoph Kleinschnitz Christoph Kleinschnitz 100319475328460016190 100319475328460016190 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Sven G Meuth Sven G Meuth 100319475328460016191 100319475328460016191 No Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany Department of Neurology and Institute for Translational Neurology and Neurology Clinic, Münster University, Münster, Germany