@article{NeuhausBurekDjuzenovaetal.2012,
  author    = {Neuhaus, Winfried and Burek, Malgorzata and Djuzenova, Cholpon C and Thal, Serge C and Koepsell, Hermann and Roewer, Norbert and F{\"o}rster, Carola Y},
  title     = {Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the up-regulation of glucose uptake after subsequent reoxygenation in brain endothelial cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67241},
  year      = {2012},
  abstract  = {During stroke the blood-brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7- fold after 6 h OGD, which was significantly reduced by 10 μM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907\% after 6 h OGD and was still higher (210\%) after the 20 h reoxygenation phase compared to normoxia. Ten micromolar MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.},
  subject      = {Blut-Hirn-Schranke},
  language  = {en}
}
@article{ThalSmetakHayashietal.2022,
  author    = {Thal, Serge C. and Smetak, Manuel and Hayashi, Kentaro and F{\"o}rster, Carola Y.},
  title     = {Hemorrhagic cerebral insults and secondary Takotsubo syndrome: findings in a novel in vitro model using human blood samples},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {19},
  issn      = {1422-0067},
  doi       = {10.3390/ijms231911557},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288305},
  year      = {2022},
  abstract  = {Intracranial hemorrhage results in devastating forms of cerebral damage. Frequently, these results also present with cardiac dysfunction ranging from ECG changes to Takotsubo syndrome (TTS). This suggests that intracranial bleeding due to subarachnoid hemorrhage (SAH) disrupts the neuro-cardiac axis leading to neurogenic stress cardiomyopathy (NSC) of different degrees. Following this notion, SAH and secondary TTS could be directly linked, thus contributing to poor outcomes. We set out to test if blood circulation is the driver of the brain-heart axis by investigating serum samples of TTS patients. We present a novel in vitro model combining SAH and secondary TTS to mimic the effects of blood or serum, respectively, on blood-brain barrier (BBB) integrity using in vitro monolayers of an established murine model. We consistently demonstrated decreased monolayer integrity and confirmed reduced Claudin-5 and Occludin levels by RT-qPCR and Western blot and morphological reorganization of actin filaments in endothelial cells. Both tight junction proteins show a time-dependent reduction. Our findings highlight a faster and more prominent disintegration of BBB in the presence of TTS and support the importance of the bloodstream as a causal link between intracerebral bleeding and cardiac dysfunction. This may represent potential targets for future therapeutic inventions in SAH and TTS.},
  language  = {en}
}
@article{GriemertSchwarzmaierHummeletal.2019,
  author    = {Griemert, Eva-Verena and Schwarzmaier, Susanne M. and Hummel, Regina and G{\"o}lz, Christina and Yang, Dong and Neuhaus, Winfried and Burek, Malgorzata and F{\"o}rster, Carola Y. and Petkovic, Ivan and Trabold, Raimund and Plesnila, Nikolaus and Engelhard, Kristin and Sch{\"a}fer, Michael K. and Thal, Serge C.},
  title     = {Plasminogen activator inhibitor-1 augments damage by impairing fibrinolysis after traumatic brain injury},
  series = {Annals of Neurology},
  volume    = {85},
  journal   = {Annals of Neurology},
  doi       = {10.1002/ana.25458},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228682},
  pages     = {667-680},
  year      = {2019},
  abstract  = {Objective Plasminogen activator inhibitor-1 (PAI-1) is the key endogenous inhibitor of fibrinolysis, and enhances clot formation after injury. In traumatic brain injury, dysregulation of fibrinolysis may lead to sustained microthrombosis and accelerated lesion expansion. In the present study, we hypothesized that PAI-1 mediates post-traumatic malfunction of coagulation, with inhibition or genetic depletion of PAI-1 attenuating clot formation and lesion expansion after brain trauma. Methods We evaluated PAI-1 as a possible new target in a mouse controlled cortical impact (CCI) model of traumatic brain injury. We performed the pharmacological inhibition of PAI-1 with PAI-039 and stimulation by tranexamic acid, and we confirmed our results in PAI-1-deficient animals. Results PAI-1 mRNA was time-dependently upregulated, with a 305-fold peak 12 hours after CCI, which effectively counteracted the 2- to 3-fold increase in cerebral tissue-type/urokinase plasminogen activator expression. PAI-039 reduced brain lesion volume by 26\% at 24 hours and 43\% at 5 days after insult. This treatment also attenuated neuronal apoptosis and improved neurofunctional outcome. Moreover, intravital microscopy demonstrated reduced post-traumatic thrombus formation in the pericontusional cortical microvasculature. In PAI-1-deficient mice, the therapeutic effect of PAI-039 was absent. These mice also displayed 13\% reduced brain damage compared with wild type. In contrast, inhibition of fibrinolysis with tranexamic acid increased lesion volume by 25\% compared with vehicle. Interpretation This study identifies impaired fibrinolysis as a critical process in post-traumatic secondary brain damage and suggests that PAI-1 may be a central endogenous inhibitor of the fibrinolytic pathway, promoting a procoagulatory state and clot formation in the cerebral microvasculature. Ann Neurol 2019;85:667-680},
  language  = {en}
}