TY  - JOUR
A1  - Thal, Serge C.
A1  - Smetak, Manuel
A1  - Hayashi, Kentaro
A1  - Förster, Carola Y.
T1  - Hemorrhagic cerebral insults and secondary Takotsubo syndrome: findings in a novel in vitro model using human blood samples
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - Takotsubo syndrome
KW  - subarachnoid hemorrhage
KW  - inflammation
KW  - in vitro
KW  - blood
KW  - blood–brain barrier
KW  - human
KW  - patient
KW  - endothelial cells
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288305
SN  - 1422-0067
VL  - 23
IS  - 19
ER  - 
TY  - JOUR
A1  - Neuhaus, Winfried
A1  - Schlundt, Marian
A1  - Fehrholz, Markus
A1  - Ehrke, Alexander
A1  - Kunzmann, Steffen
A1  - Liebner, Stefan
A1  - Speer, Christian P.
A1  - Förster, Carola Y.
T1  - Multiple antenatal dexamethasone treatment alters brain vessel differentiation in newborn mouse pups
JF  - PLoS ONE
N2  - Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB) phenotype, focusing on molecular marker analysis. The major findings were that in total brains on postnatal day (PN) 4 triple antenatal dexamethasone treatment significantly downregulated the tight junction protein claudin-5, the endothelial marker Pecam-1/CD31, the glucocorticoid receptor, the NR1 subunit of the N-methyl-D-aspartate receptor, and Abc transporters (Abcb1a, Abcg2 Abcc4). Less pronounced effects were found after single antenatal dexamethasone treatment and in PN10 samples. Comparisons of total brain samples with isolated brain endothelial cells together with the stainings for Pecam-1/CD31 and claudin-5 led to the assumption that the morphology of brain vessels is affected by antenatal dexamethasone treatment at PN4. On the mRNA level markers for angiogenesis, the sonic hedgehog and the Wnt pathway were downregulated in PN4 samples, suggesting fundamental changes in brain vascularization and/or differentiation. In conclusion, we provided a first comprehensive molecular basis for the adverse effects of multiple antenatal dexamethasone treatment on brain vessel differentiation.
KW  - preterm birth
KW  - fetal lung
KW  - corticosteroids
KW  - glucocorticoids
KW  - exposure
KW  - endothelial cells
KW  - in vitro
KW  - barrier
KW  - expression
KW  - rat
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148268
VL  - 10
IS  - 8
ER  -