@phdthesis{Gehringer2017,
  author    = {Gehringer, Rebekka},
  title     = {Periphere Mechanismen von Elektroakupunktur bei Entz{\"u}ndungsschmerz},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153261},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Die Grundlage f{\"u}r diese Arbeit bildete ein Modell mit CFA-(komplettes Freundsches Adjuvant) induziertem Entz{\"u}ndungsschmerz in Ratten, bei denen eine zweimalige Behandlung mit Elektroakupunktur zu einer langanhaltenden Antinozizeption f{\"u}hrte, welche abh{\"a}ngig von peripheren Opioiden war. In einem n{\"a}chsten Schritt sollten nun die durch Akupunktur vermittelten Zytokin- und Chemokinver{\"a}nderungen untersucht und deren Beitrag zu den antinozizeptiven und anttiinflammatorischen Mechanismen gekl{\"a}rt werden. Mittels ELISA und PCR wurden die Protein- und mRNA-Level der klassischen Zytokine und des Chemokins CXCL10 bestimmt. CXCL10, welches durch Elektroakupunktur sowohl auf Transkriptions- als auch auf Translationsebene hochreguliert wurde, ist notwendig f{\"u}r die Rekrutierung β-Endorphin haltiger Makrophagen in das entz{\"u}ndete Gewebe und f{\"u}r die antinozizeptive Wirkung der Akupunkturbehandlung. Ein antiinflammatorischer Effekt der Akupunkturbehandlung {\"a}ußerte sich durch die Reduktion von TNF-α und IL-1β und ein erh{\"o}htes IL-13. Das einzige hochregulierte proinflammatorische Zytokin war IFN-γ. Ein Teil der entz{\"u}ndungshemmenden Wirkung, die Reduktion der proinflammatorischen Zytokine TNF-α und IL-1β, wird durch Adenosin-2B-Rezeptoren vermittelt, welche bekannt sind f{\"u}r ihre Rolle in der „Deaktivierung" IFN-γ-stimulierter Makrophagen. Diese Ergebnisse verweisen auf die bisher unbekannte Verbindung zwischen chemokinvermittelter peripherer, opioidabh{\"a}ngiger Antinozizeption durch Elektroakupunktur. Sie erweitern das Verst{\"a}ndnis f{\"u}r das Zusammenspiel von Immunzellen, Adenosin und Akupunktur. Weitere Untersuchungen sind notwendig, um neuroimmunologische Verbindungen zu kl{\"a}ren und die Wirkungen durch die Nadelinsertion mit Effekten in der entfernten Rattenpfote besser zu verstehen.},
  subject      = {Elektroakupunktur},
  language  = {de}
}
@phdthesis{Deppermann2017,
  author    = {Deppermann, Carsten},
  title     = {The role of platelet granules in thrombosis, hemostasis, stroke and inflammation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121010},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Platelets are small anucleate cell fragments derived from bone marrow megakaryocytes (MKs) and are important players in hemostasis and thrombosis. Platelet granules store factors which are released upon activation. There are three major types of platelet granules: alpha-granules, dense granules and lysosomes. While dense granules contain non-proteinacious factors which support platelet aggregation and adhesion, platelet alpha-granules contain more than 300 different proteins involved in various functions such as inflammation, wound healing and the maintenanceof vascular integrity, however, their functional significance in vivo remains unknown. This thesis summarizes analyses using three mouse models generated to investigate the role of platelet granules in thrombosis, hemostasis, stroke and inflammation. Unc13d-/- mice displayed defective platelet dense granule secretion, which resulted in abrogated thrombosis and hemostasis. Remarkably, Munc13-4-deficient mice were profoundly protected from infarct progression following transient middle cerebral artery occlusion (tMCAO) and this was not associated with increased intracranial bleeding indicating an essential involvementof dense granule secretion in infarct progression but not intracranial hemostasis during acute stroke with obvious therapeutic implications. In the second part of this thesis, the role of platelet alpha-granules was investigated using the Nbeal2-/- mouse. Mutations in NBEAL2 have been linked to the gray platelet syndrome (GPS), a rare inherited bleeding disorder. Nbeal2-/- mice displayed the characteristics of human GPS, with defective alpha-granule biogenesis in MKs and their absence from platelets. Nbeal2-deficiency did not affect MK differentiation and proplatelet formation in vitro or platelet life span in vivo. Nbeal2-/- platelets displayed impaired adhesion, aggregation, and coagulant activity ex vivo that translated into defective arterial thrombus formation and protection from thrombo-inflammatory brain infarction in vivo. In a model of skin wound repair, Nbeal2-/- mice exhibited impaired development of functional granulation tissue due to severely reduced differentiation of myofibroblasts. In the third part, the effects of combined deficiency of alpha- and dense granule secretion were analyzed using Unc13d-/-/Nbeal2-/- mice. Platelets of these mice showed impaired aggregation and adhesion to collagen under flow ex vivo, which translated into infinite tail bleeding times and severely defective arterial thrombus formation in vivo. When subjected to in vivo models of skin or lung inflammation, the double mutant mice showed no signs of hemorrhage. In contrast, lack of platelet granule release resulted in impaired vascular integrity in the ischemic brain following tMCAO leading to increased mortality. This indicates that while defective dense granule secretion or the paucity of alpha-granules alone have no effect on vascular integrity after stroke, the combination of both impairs vascular integrity and causes an increase in mortality.},
  subject      = {Thrombozyten},
  language  = {en}
}