TY  - JOUR
A1  - Bieber, Michael
A1  - Foerster, Kathrin I.
A1  - Haefeli, Walter E.
A1  - Pham, Mirko
A1  - Schuhmann, Michael K.
A1  - Kraft, Peter
T1  - Treatment with edoxaban attenuates acute stroke severity in mice by reducing blood–brain barrier damage and inflammation
JF  - International Journal of Molecular Sciences
N2  - Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood–brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted.
KW  - edoxaban
KW  - thrombo-inflammation
KW  - blood–brain barrier
KW  - tMCAO
KW  - experimental stroke
KW  - hemorrhagic transformation
KW  - NOAC
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284481
SN  - 1422-0067
VL  - 22
IS  - 18
ER  - 
TY  - JOUR
A1  - Salvador, Ellaine
A1  - Burek, Malgorzata
A1  - Löhr, Mario
A1  - Nagai, Michiaki
A1  - Hagemann, Carsten
A1  - Förster, Carola Y.
T1  - Senescence and associated blood-brain barrier alterations in vitro
JF  - Histochemistry and Cell Biology
N2  - Progressive deterioration of the central nervous system (CNS) is commonly associated with aging. An important component of the neurovasculature is the blood-brain barrier (BBB), majorly made up of endothelial cells joined together by intercellular junctions. The relationship between senescence and changes in the BBB has not yet been thoroughly explored. Moreover, the lack of in vitro models for the study of the mechanisms involved in those changes impede further and more in-depth investigations in the field. For this reason, we herein present an in vitro model of the senescent BBB and an initial attempt to identify senescence-associated alterations within.
KW  - senescence
KW  - in vitro model
KW  - aging
KW  - CNS diseases
KW  - blood–brain barrier
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267435
SN  - 1432-119X
VL  - 156
IS  - 3
ER  - 
TY  - JOUR
A1  - Shityakov, Sergey
A1  - Hayashi, Kentaro
A1  - Störk, Stefan
A1  - Scheper, Verena
A1  - Lenarz, Thomas
A1  - Förster, Carola Y.
T1  - The conspicuous link between ear, brain and heart − Could neurotrophin-treatment of age-related hearing loss help prevent Alzheimer's disease and associated amyloid cardiomyopathy?
JF  - Biomolecules
N2  - Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction and cognitive decline. While the deposition of amyloid β peptide (Aβ) and the formation of neurofibrillary tangles (NFTs) are the pathological hallmarks of AD-affected brains, the majority of cases exhibits a combination of comorbidities that ultimately lead to multi-organ failure. Of particular interest, it can be demonstrated that Aβ pathology is present in the hearts of patients with AD, while the formation of NFT in the auditory system can be detected much earlier than the onset of symptoms. Progressive hearing impairment may beget social isolation and accelerate cognitive decline and increase the risk of developing dementia. The current review discusses the concept of a brain–ear–heart axis by which Aβ and NFT inhibition could be achieved through targeted supplementation of neurotrophic factors to the cochlea and the brain. Such amyloid inhibition might also indirectly affect amyloid accumulation in the heart, thus reducing the risk of developing AD-associated amyloid cardiomyopathy and cardiovascular disease.
KW  - Alzheimer's disease
KW  - amyloid cardiomyopathy
KW  - heart failure
KW  - age-related hearing loss
KW  - neurotrophins
KW  - blood–brain barrier
KW  - blood–labyrinth barrier
KW  - spiral ganglion neuron
KW  - BDNF
KW  - GDNF
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241084
SN  - 2218-273X
VL  - 11
IS  - 6
ER  -