Journal Article10.1161/STROKEAHA.114.005836
Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke.
Mathias Gelderblom,Nico Melzer,Benjamin Schattling,Eva Göb,Gordon Hicking,Priyadharshini Arunachalam,Stefan Bittner,Friederike Ufer,Alexander M. Herrmann,Christian Bernreuther,Markus Glatzel,Christian Gerloff,Christoph Kleinschnitz,Sven G. Meuth,Manuel A. Friese,Tim Magnus +15 more
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TL;DR: Although a neuroprotective effect of Trpm2 in vitro is well known, this work can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells.
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Abstract: Background and Purpose—Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca2+, hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. Methods—In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. Results—Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2-deficient mice. Bo...
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References
The immunology of stroke: from mechanisms to translation
TL;DR: Gaining a better understanding of the reciprocal interaction between the immune system and the ischemic brain is essential to harness the full therapeutic potential of the immunology of stroke.
Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke
Mathias Gelderblom,Frank Leypoldt,Karin Steinbach,Doerthe Behrens,Chi-Un Choe,Dominic A. Siler,Thiruma V. Arumugam,Ellen Orthey,Christian Gerloff,Eva Tolosa,Tim Magnus +10 more
TL;DR: The peculiar activation pattern and massive increase of antigen-presenting cells in temporal conjunction with regulatory cells might provide additional insight into poststroke immune regulation.
991
The immunology of acute stroke.
Ángel Chamorro,Andreas Meisel,Anna M. Planas,Xabier Urra,Diederik van de Beek,Roland Veltkamp +5 more
TL;DR: The multifaceted role of the immune system in the pathophysiology of acute stroke is discussed, with increased incidence of infections observed after acute stroke, and might result from activation of long-distance feedback loops between the CNS and peripheral immune organs.
607
TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration
Shinichiro Yamamoto,Shunichi Shimizu,Shigeki Kiyonaka,Nobuaki Takahashi,Teruaki Wajima,Yuji Hara,Takaharu Negoro,Toshihito Hiroi,Yuji Kiuchi,Takaharu Okada,Shuji Kaneko,Ingo Lange,Andrea Fleig,Reinhold Penner,Miyuki Nishi,Hiroshi Takeshima,Yasuo Mori +16 more
TL;DR: It is shown that the plasma membrane Ca2+-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes, which aggravates inflammation and is proposed as a new therapeutic strategy for treating inflammatory diseases.
Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke
Yang-Wei Fann,S-Y Lee,Silvia Manzanero,Sung-Chun Tang,Mathias Gelderblom,Prasad Chunduri,Christian Bernreuther,Markus Glatzel,Yi-Lin Cheng,John Thundyil,Alexander Widiapradja,Ker Zhing Lok,S L Foo,Y-C Wang Wang,Y-I Li,Grant R Drummond,Milan Basta,Tim Magnus,Dong-Gyu Jo,Mark P. Mattson,Christopher G. Sobey,Thiruma V. Arumugam,Thiruma V. Arumugam,Thiruma V. Arumugam +23 more
TL;DR: Evidence is provided that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke, and that IVIg treatment can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that targetinflammasome assembly and activity.