Biology subjects

Kriauciunaite, K.

Publications and source records attributed to Kriauciunaite, K..

3 recordsLinked to original sources

bioRxiv2023

Plasma of COVID-19 patients does not alter electrical resistance of human endothelial blood-brain barrier in vitro.

The pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathological impairment of blood-brain barrier (BBB) contributes to the development of neuropathology during COVID-19 progression. In the present study we used human induced pluripotent stem cells-derived brain endothelial cells (iBECs) to study the effects of blood plasma derived from COVID-19 patients on the BBB integrity in vitro. We also performed a comprehensive analysis of the cytokine and chemokine profiles in the plasma of COVID-19 patients, healthy and recovered individuals. We found significantly increased levels of interferon {gamma}-induced protein 10 kDa (IP-10), hepatocyte growth factor (HGF), and interleukin-18 (IL-18) in the plasma of COVID-19 patients. However, blood plasma from COVID-19 patients did not affect transendothelial electrical resistance (TEER) in iBEC monolayers. Our results demonstrate that COVID-19-associated blood plasma inflammatory factors do not impair BBB integrity directly and suggest that pathological remodelling of BBB during COVID-19 may occur through indirect mechanisms.

neuroscience↗

bioRxiv2021

Concentration-dependent duality of bFGF in regulation of barrier properties of human brain endothelial cells

Multiple paracrine factors regulate barrier properties of human brain capillary endothelial cells (BCECs). Understanding precise mode of action of these factors remains a challenging task because of the limited availability of functionally competent BCECs and use of serum-containing medium. In the present study we employed defined protocol for producing BCECs from human inducible pluripotent stem cells. We found that autocrine secretion of basic fibroblast growth factor (bFGF) is necessary for the establishment a tight BCECs barrier, as revealed by measurements of trans-endothelial electric resistance (TEER). In contrast, exogenous bFGF in concentrations exceeding 4 ng/ml inhibited TEER and proliferation of BCECs in a concentration-dependent manner. Exogenous bFGF did not significantly affect expression and distribution of tight junction proteins claudin-5, occludin and ZO-1. Treatment with FGF receptor blocker PD173074 (15 M) suppressed inhibitory effects of bFGF and induced nuclear translocation of protein ZO-1. Inhibition of phosphoinositide 3-Kinase (PI-3K) with LY294002 (25 M) significantly potentiated inhibitory effect of bFGF on TEER indicating that PI-3K signalling pathway partially suppress inhibitory effects of bFGF on TEER. In conclusion we show that autocrine bFGF secretion is necessary for the proper barrier function of BCECs, whereas exogenous bFGF suppresses barrier resistance in a concentration-dependent manner. Our findings demonstrate a dual role for bFGF in the regulation of BCEC barrier function.

molecular biology↗

bioRxiv2020

Immortalised hippocampal astrocytes from 3xTG-AD mice fail to support BBB integrity in vitro: Role of extracellular vesicles in glial-endothelial communication

Impairments of the blood brain barrier (BBB) and vascular dysfunction contribute to Alzheimers disease (AD) from the earliest stages. However, the effects of AD-affected astrocytes on the BBB remain largely unexplored. In the present study we created an in vitro BBB using human immortalised endothelial cells in combination with immortalised astroglial cell lines from the hippocampus of 3xTG-AD and wild-type mice (3Tg-iAstro and WT-iAstro, respectively). We found that co-culturing endothelial monolayers with WT-iAstro up-regulates expression of endothelial tight junction proteins (claudin-5, occludin, ZO-1) and increases the trans-endothelial electrical resistance (TEER). In contrast, co-culturing with 3Tg-iAstro does not affect expression of tight junction proteins and does not change the TEER of endothelial monolayers. The same in vitro model has been used to evaluate the effects of extracellular vesicles (EVs) derived from the WT-iAstro and 3Tg-iAstro. The EVs derived from WT-iAstro increased TEER and up-regulated expression of tight junction proteins, whereas EVs from 3Tg-iAstro were ineffective. In conclusion, we show for the first time that immortalised hippocampal astrocytes from 3xTG-AD mice exhibit impaired capacity to support BBB integrity in vitro through paracrine mechanisms and may represent an important factor underlying vascular abnormalities during development of AD.

neuroscience↗