cerebral ischemia; inflammation; hypercholesterolemia; photoacoustic imaging; magnetic resonance imaging; neutrophils; near-infrared fluorescence imaging
Probst Jasmin, Rohner Marco, Zahn Malin, Piccirelli Marco, Pangalu Athina, Luft Andreas, Deistung Andreas, Klohs Jan, Wegener Susanne (2021), Quantitative susceptibility mapping in ischemic stroke patients after successful recanalization, in Scientific Reports
, 11(1), 16038-16038.
Louloudis Georgios, Ambrosini Samuele, Paneni Francesco, Camici Giovanni G., Benke Dietmar, Klohs Jan (2021), Adeno-Associated Virus-Mediated Gain-of-Function mPCSK9 Expression in the Mouse Induces Hypercholesterolemia, Monocytosis, Neutrophilia, and a Hypercoagulative State, in Frontiers in Cardiovascular Medicine
, 8, 1.
Ni Ruiqing, Villois Alessia, Dean-Ben Xose Luis, Chen Zhenyue, Vaas Markus, Stavrakis Stavros, Shi Gloria, deMello Andrew, Ran Chongzhao, Razansky Daniel, Arosio Paolo, Klohs Jan (2021), In-vitro and in-vivo characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice, in Photoacoustics
, 23, 100285-100285.
Klohs Jan, Hirt Ann M. (2021), Investigation of the magnetic susceptibility properties of fresh and fixed mouse heart, liver, skeletal muscle and brain tissue, in Physica Medica
, 88, 37-44.
Massalimova Aidana, Ni Ruiqing, Nitsch Roger M., Reisert Marco, von Elverfeldt Dominik, Klohs Jan (2021), Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy, in Neurodegenerative Diseases
Razansky Daniel, Klohs Jan, Ni Ruiqing (2021), Multi-scale optoacoustic molecular imaging of brain diseases, in European Journal of Nuclear Medicine and Molecular Imaging
Riabinska Arina, Zille Marietta, Terzi Menderes Yusuf, Cordell Ryan, Nieminen-Kelhä Melina, Klohs Jan, Piña Ana Luisa (2020), Pigment Epithelium-Derived Factor Improves Paracellular Blood–Brain Barrier Integrity in the Normal and Ischemic Mouse Brain, in Cellular and Molecular Neurobiology
, 40(5), 751-764.
Ni Ruiqing, Zarb Yvette, Kuhn Gisela A., Müller Ralph, Yundung Yankey, Nitsch Roger M., Kulic Luka, Keller Annika, Klohs Jan (2020), SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy, in Magnetic Resonance Materials in Physics, Biology and Medicine
Klohs Jan (2020), An Integrated View on Vascular Dysfunction in Alzheimer’s Disease, in Neurodegenerative Diseases
, 19(3-4), 109-127.
Zarb Yvette, Weber-Stadlbauer Ulrike, Kirschenbaum Daniel, Kindler Diana Rita, Richetto Juliet, Keller Daniel, Rademakers Rosa, Dickson Dennis W, Pasch Andreas, Byzova Tatiana, Nahar Khayrun, Voigt Fabian F, Helmchen Fritjof, Boss Andreas, Aguzzi Adriano, Klohs Jan, Keller Annika (2019), Ossified blood vessels in primary familial brain calcification elicit a neurotoxic astrocyte response, in Brain
, 142(4), 885-902.
Ni Ruiqing, Kindler Diana Rita, Waag Rebecca, Rouault Marie, Ravikumar Priyanka, Nitsch Roger, Rudin Markus, Camici Giovanni G., Liberale Luca, Kulic Luka, Klohs Jan (2019), fMRI Reveals Mitigation of Cerebrovascular Dysfunction by Bradykinin Receptors 1 and 2 Inhibitor Noscapine in a Mouse Model of Cerebral Amyloidosis, in Frontiers in Aging Neuroscience
, 11, 27.
Enzmann Gaby U., Pavlidou Sofia, Vaas Markus, Klohs Jan, Engelhardt Britta (2018), ICAM-1null C57BL/6 Mice Are Not Protected from Experimental Ischemic Stroke, in Translational Stroke Research
, 9(6), 608-621.
Acker Güliz, Piper Sophie Käthe, Datwyler Anna Lena, Broggini Thomas, Kremenetskaia Irina, Nieminen-Kelhä Melina, Lips Janet, Harms Ulrike, Mueller Susanne, Lättig-Tünnemann Gilla, Trachsel Eveline, Palumbo Alessandro, Neri Dario, Klohs Jan, Endres Matthias, Vajkoczy Peter, Harms Christoph, Czabanka Marcus (2018), Targeting the extradomain A of fibronectin allows identification of vascular resistance to antiangiogenic therapy in experimental glioma, in Oncotarget
, 9(45), 27760-27772.
Ni Ruiqing, Rudin Markus, Klohs Jan (2018), Cortical hypoperfusion and reduced cerebral metabolic rate of oxygen in the arcAβ mouse model of Alzheimer’s disease, in Photoacoustics
, 10, 38-47.
Diaz-Cañestro Candela, Merlini Mario, Bonetti Nicole R., Liberale Luca, Wüst Patricia, Briand-Schumacher Sylvie, Klohs Jan, Costantino Sara, Miranda Melroy, Schoedon-Geiser Gabriele, Kullak-Ublick Gerd A., Akhmedov Alexander, Paneni Francesco, Beer Jürg H., Lüscher Thomas F., Camici Giovanni G. (2018), Sirtuin 5 as a novel target to blunt blood–brain barrier damage induced by cerebral ischemia/reperfusion injury, in International Journal of Cardiology
, 260, 148-155.
Ni Ruiqing, Vaas Markus, Ren Wuwei, Klohs Jan (2018), Noninvasive detection of acute cerebral hypoxia and subsequent matrix-metalloproteinase activity in a mouse model of cerebral ischemia using multispectral-optoacoustic-tomography, in Neurophotonics
, 5(01), 1-1.
Therapeutic options in acute ischemic stroke are limited and rely solely on pharmacological and mechanical recanalization strategies within a short therapeutic window after stroke. Despite high recanalization rates clinical outcome in these patients is highly variable. In stroke patients, hypercholesterolemia (HC) is a highly prevalent co-morbidity which has been shown to negatively impact clinical outcome after ischemic stroke. However, the mechanisms by which HC affects the ischemic injury remain largely unknown.Experimental studies have shown that HC induces systemic immune changes. It increases the number of circulating leukocytes; triggers activation of monocytes and neutrophils, cytokine production, and release of coagulation factors. Neutrophils have a particularly important role in this immune response. HC increases neutrophil production, primes neutrophils and leads to an increase in superoxide production and degranulation. Given the importance of thromboinflammatory processes in mediating blood-brain barrier damage, hemorrhagic transformation and secondary microvascular thrombosis after stroke, priming of neutrophils in HC might constitute an important way in exacerbating ischemic brain and reperfusion injury, but experimental evidence is still lacking.We herein propose to test the hypotheses that HC induces neutrophilia and primes neutrophils, and that this condition exacerbates ischemic tissue injury and worsens neurological outcome following cerebral ischemia and reperfusion. We will verify these hypotheses in patients with ischemic stroke, and then use preclinical models of human disease and advanced imaging techniques to elucidate the mechanisms by which neutrophils affect ischemic tissue damage and outcome, with a focus on hemodynamic function and vascular integrity. Specifically, we will address:1. Does HC induce neutrophilia, primes neutrophils and is it linked to measures of the thromboinflammatory response in patients with ischemic stroke and mice with experimental stroke?2. Do neutrophil extracellular traps mediate secondary microvascular thrombosis and prevent tissue reperfusion?3. Does current pharmacological thrombolysis following cerebral ischemia under HC conditions aggravate impairment of the blood-brain barrier and hemorrhagic transformation by enhancing reactive oxygen species production and degranulation?This project will bring novel insight into the role of HC on the pathophysiology of stroke. We predict that there are differences in the neutrophil response and their downstream-mediated processes in stroke patients with HC, where immunomodulatory therapy might be required to ameliorate ischemic and reperfusion injury and to improve outcome in such patients.