A5056821347- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Platelet Disorders and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Adhesion Molecules Research
- Blood Coagulation and Thrombosis Mechanisms
- Mast cells and histamine
- Complement system in diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Acute Ischemic Stroke Management
- S100 Proteins and Annexins
- Antiplatelet Therapy and Cardiovascular Diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Tryptophan and brain disorders
- Vascular Malformations Diagnosis and Treatment
- Exercise and Physiological Responses
- Atherosclerosis and Cardiovascular Diseases
- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Phosphodiesterase function and regulation
- Synthesis and Catalytic Reactions
- Intracerebral and Subarachnoid Hemorrhage Research
- Neurological Disease Mechanisms and Treatments
- Anesthesia and Neurotoxicity Research
- Animal testing and alternatives
University of Würzburg
2016-2021
Universitätsklinikum Würzburg
2016-2019
University Hospital Münster
2018
Research Institute for Chromatography
2016
KU Leuven
2016
University of Regensburg
2016
University of Duisburg-Essen
2016
University of Tübingen
2016
Significance Why the brain is uniquely sensitive to hypoxia and which cells are involved incompletely understood. Here we identify that, upon ischemic stroke, in endothelial neurons reactive oxygen-forming NADPH oxidase 4 (NOX4) causes breakdown of BBB neuronal cell death. This mechanism unique not found other forms ischemia body. Genetic deletion either type (endothelial or neuronal) pharmacological inhibition NOX4 leads a significant reduction infarct volume direct neuroprotection....
Background and Purpose- The selection of appropriate neurological scores tests is crucial for the evaluation stroke consequences. validity reliability deficit has repeatedly been questioned in ischemic models past. Methods- In 198 male mice exposed to transient intraluminal middle cerebral artery occlusion, we examined 11 (Bederson score 0-3, Bederson 0-4, 0-5, modified severity [0-14], subjective overall impression [0-10], or simple tests: grip test, latency move body length pole wire...
Ischemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal the occlusion being only therapeutic option. Reperfusion bears risk an acute deleterious calcium-dependent breakdown blood-brain barrier. Its mechanism, however, unknown. Here, we identified type 5 NADPH oxidase (NOX5), calcium-activated, ROS-forming enzyme, as missing link. Using humanized knockin (KI) mouse model and in vitro organotypic cultures, found that reoxygenation calcium...
Network medicine utilizes common genetic origins, markers and co-morbidities to uncover mechanistic links between diseases. These can be summarized in the diseasome, a comprehensive network of disease-disease relationships clusters. The diseasome has been influential during past decade, although most its are not followed up experimentally. Here, we investigate high prevalence unmet medical need cluster disease phenotypes linked cyclic GMP. Hitherto, central cGMP-forming enzyme, soluble...
It is known that both platelets and coagulation strongly influence infarct progression after ischemic stroke, but the mechanisms their interplay are unknown. Our aim was to assess contribution of procoagulant platelet surface, thus platelet-driven thrombin generation, thromboinflammation in brain.We present characterization a novel megakaryocyte-specific TMEM16F (anoctamin 6) knockout mouse. Reflecting Scott syndrome, from mouse had significant reduction characteristics altered fibrin...
Significance Transendothelial trafficking of immune cells into the central nervous system (CNS) is a pathophysiological hallmark neuroinflammatory disorders like multiple sclerosis (MS). Recent evidence suggests that coagulation and kallikrein-kinin cascade might participate in this process. Here, we identify plasma kallikrein (KK) as direct modulator blood–brain barrier function protease-activated receptor-2–dependent manner, amplifying leukocyte CNS. Consequently, deficiency prekallikrein...
Objective— Activation of platelets by subendothelial collagen results in an increase cytosolic Ca 2+ concentration ([Ca ] i ) and is followed platelet activation thrombus formation that may lead to vascular occlusion. The present study determined the role phosphoinositide-dependent protein kinase 1 (PDK1) collagen-dependent signaling ischemic stroke vivo. Approach Results— Platelet with receptor glycoprotein VI agonists collagen-related peptide or convulxin resulted a significant PDK1...
Endothelium protection is critical, because of the impact vascular leakage and edema on pathological conditions such as brain ischemia. Whereas deficiency class II phosphoinositide 3‐kinase alpha (PI3KC2α) results in an increase permeability, we uncover a crucial role beta isoform (PI3KC2β) loss endothelial barrier integrity following injury. Here, studied PI3KC2β permeability endosomal trafficking vitro vivo ischemic stroke. Mice with inactive showed against edema, cerebral infarction,...
Abstract Ischemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal the occlusion being only therapeutic options. Reperfusion bears risk an acute deleterious calcium-dependent breakdown blood-brain-barrier. Its mechanism, however, unknown. Here we identify type 5 NADPH oxidase (NOX5), calcium-activated, reactive oxygen species (ROS)-forming enzyme as missing link. Using humanised knock-in mouse model and in vitro organotypic cultures, find...