@article{SchuhmannBieberFrankeetal.2021,
  author    = {Schuhmann, Michael K. and Bieber, Michael and Franke, Maximilian and Kollikowski, Alexander M. and Stegner, David and Heinze, Katrin G. and Nieswandt, Bernhard and Pham, Mirko and Stoll, Guido},
  title     = {Platelets and lymphocytes drive progressive penumbral tissue loss during middle cerebral artery occlusion in mice},
  series = {Journal of Neuroinflammation},
  volume    = {18},
  journal   = {Journal of Neuroinflammation},
  number    = {1},
  doi       = {10.1186/s12974-021-02095-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259172},
  pages     = {46},
  year      = {2021},
  abstract  = {Background In acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood. Methods To address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1\(^{-/-}\) mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion. Results We show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion. Conclusions Progressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.},
  language  = {en}
}
@article{ShaikhVargasMokhtarietal.2021,
  author    = {Shaikh, Haroon and Vargas, Juan Gamboa and Mokhtari, Zeinab and Jarick, Katja J. and Ulbrich, Maria and Mosca, Josefina Pe{\~n}a and Viera, Estibaliz Arellano and Graf, Caroline and Le, Duc-Dung and Heinze, Katrin G. and B{\"u}ttner-Herold, Maike and Rosenwald, Andreas and Pezoldt, Joern and Huehn, Jochen and Beilhack, Andreas},
  title     = {Mesenteric Lymph Node Transplantation in Mice to Study Immune Responses of the Gastrointestinal Tract},
  series = {Frontiers in Immunology},
  volume    = {12},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2021.689896},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244869},
  year      = {2021},
  abstract  = {Mesenteric lymph nodes (mLNs) are sentinel sites of enteral immunosurveillance and immune homeostasis. Immune cells from the gastrointestinal tract (GIT) are constantly recruited to the mLNs in steady-state and under inflammatory conditions resulting in the induction of tolerance and immune cells activation, respectively. Surgical dissection and transplantation of lymph nodes (LN) is a technique that has supported seminal work to study LN function and is useful to investigate resident stromal and endothelial cell biology and their cellular interactions in experimental disease models. Here, we provide a detailed protocol of syngeneic mLN transplantation and report assays to analyze effective mLN engraftment in congenic recipients. Transplanted mLNs allow to study T cell activation and proliferation in preclinical mouse models. Donor mLNs proved viable and functional after surgical transplantation and regenerated blood and lymphatic vessels. Immune cells from the host completely colonized the transplanted mLNs within 7-8 weeks after the surgical intervention. After allogeneic hematopoietic cell transplantation (allo-HCT), adoptively transferred allogeneic CD4+ T cells from FVB/N (H-2q) mice homed to the transplanted mLNs in C57BL/6 (H-2b) recipients during the initiation phase of acute graft-versus-host disease (aGvHD). These CD4+ T cells retained full proliferative capacity and upregulated effector and gut homing molecules comparable to those in mLNs from unmanipulated wild-type recipients. Wild type mLNs transplanted into MHCII deficient syngeneic hosts sufficed to activate alloreactive T cells upon allogeneic hematopoietic cell transplantation, even in the absence of MHCII+ CD11c+ myeloid cells. These data support that orthotopically transplanted mLNs maintain physiological functions after transplantation. The technique of LN transplantation can be applied to study migratory and resident cell compartment interactions in mLNs as well as immune reactions from and to the gut under inflammatory and non-inflammatory conditions.},
  language  = {en}
}
@article{GoebVollZimmermannetal.2021,
  author    = {G{\"o}b, Vanessa and Voll, Maximilian G. and Zimmermann, Lena and Hemmen, Katharina and Stoll, Guido and Nieswandt, Bernhard and Schuhmann, Michael K. and Heinze, Katrin G. and Stegner, David},
  title     = {Infarct growth precedes cerebral thrombosis following experimental stroke in mice},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-02360-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265791},
  year      = {2021},
  abstract  = {Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, successful recanalization of occluded vessels is the primary therapeutic aim, but even if it is achieved, not all patients benefit. Although blockade of platelet aggregation did not prevent infarct progression, cerebral thrombosis as cause of secondary infarct growth has remained a matter of debate. As cerebral thrombi are frequently observed after experimental stroke, a thrombus-induced impairment of the brain microcirculation is considered to contribute to tissue damage. Here, we combine the model of transient middle cerebral artery occlusion (tMCAO) with light sheet fluorescence microscopy and immunohistochemistry of brain slices to investigate the kinetics of thrombus formation and infarct progression. Our data reveal that tissue damage already peaks after 8 h of reperfusion following 60 min MCAO, while cerebral thrombi are only observed at later time points. Thus, cerebral thrombosis is not causative for secondary infarct growth during ischemic stroke.},
  language  = {en}
}