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1

In vitro models of the blood-brain barrier

100%
Wilhelm I., Fazakas C., Krizbai I. A.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
The blood-brain barrier (BBB) is an active interface between the circulation and the central nervous system (CNS) with a dual function: the barrier function restricts the transport from the blood to the brain of potentially toxic or harmful substances; the carrier function is responsible for the transport of nutrients to the brain and removal of metabolites. The BBB plays a crucial role in the clinical practice as well. On the one side there is a large number of neurological disorders including cerebral ischemia, brain trauma and tumors, neurodegenerative disorders, in which the permeability of the BBB is increased. On the other hand due to the relative impermeability of the barrier many drugs are unable to reach the CNS in therapeutically relevant concentration, making the BBB one of the major impediments in the treatment of CNS disorders. The significant scientific and industrial interest in the physiology and pathology of the BBB led to the development of several in vitro models of the BBB. These models are mainly based on the culture of cerebral endothelial cells. The best in vitro models which mimic the best way the in vivo anatomical conditions are the co-culture models in which brain endothelial cells are co-cultured with astrocytes and/or pericytes. Our in vitro BBB model is characterized by high transendothelial electrical resistance (TEER regularity above 200 Ohm*cm2), low permeability and expression of several transporters. Our experiments have proven that the model is suitable for basic research and for testing the interaction between the BBB and potential drug candidates (toxicity, permeability, interaction with efflux transporters) as well.
2

In vitro models of the blood-brain barrier

100%
Wilhelm I., Fazakas C., Krizbai I.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
The blood-brain barrier (BBB) is an active interface between the circulation and the central nervous system with a dual function: the barrier function restricts the transport from blood to the brain of potentially toxic or harmful substances the carrier function is responsible for the transport of nutrients to the brain and removal of metabolites. The BBB plays a crucial role in the clinical practice as well. On the one side there are a large number of neurological disorders including cerebral ischemia, brain trauma and tumors, neurodegenerative disorders in which the permeability of the BBB is increased. On the other hand due to the relative impermeability of the barrier many drugs are unable to reach the CNS in therapeutically relevant concentration making the BBB one of the major impediments in the treatment of CNS disorders. The significant scientific and industrial interest in the physiology and pathology of the BBB led to the development of several in vitro models of the BBB. These models are mainly based on the culture of cerebral endothelial cells. The best in vitro models which mimic in the best way the in vivo anatomical conditions are the co-culture models in which the brain endothelial cells are co-cultured with astrocytes and/or pericytes. Our in vitro BBB model is characterized by high transendothelial electrical resistance (TEER regularily between 200-400 Ohm· cm2 ), low permeability and expression of different transporters. In our experiments we have investigated the effect of different extracellular factors including oxidative stress and osmotic stress on functional characteristics of the BBB. Our experiments have proven that the model is suitable for basic research and for testing the interaction between the BBB and potential drug candidates (toxicity, permeability, interaction with efflux transporters) as well.
3

Role of the blood - brain barrier in differential response to opioid peptides and morphine in mouse lines divergently bred for high and low swim stress - induced analgesia

64%
Kosson A., Krizbai I., Lesniak A., Beresewicz M., Sacharczuk M., Kosson P., Nagyoszi P., Wilhelm I., Kleczkowska P., Lipkowski A. W.
Acta Neurobiologiae Experimentalis
|
2014
|
tom 74
|
nr 1
Over 20 years ago, the Sadowski group separated two mouse lines, one with high (HA) and the other with low (LA) sensitivity to swim stress-induced analgesia (SSIA). Recently, we proposed that increased leakage of the blood-brain barrier (BBB) in the HA line created the difference in the response to SSIA. To search for further evidence for this hypothesis, differences in the levels of the BBB proteins occludin and claudin-5 were analysed. In addition, we sought to evaluate practical differences in BBB permeability by examining the antinociceptive levels in HA and LA mouse lines after i.v. administration of peptides that have limited access to the CNS. Western blot was used to analyse the differences between occludin and claudin-5. To evaluate the functional differences between the BBB of HA and LA mice, the antinociception levels of endomorphin I, biphalin and AA2016 (peptides with limited BBB permeabilities) in the tail flick test were examined. The expression levels of occludin and claudin-5 in the HA mouse line were lower than in the LA and control mice. Central antinociception of the opioid peptides were significantly higher in the HA line than in the LA and control lines. Our data support the hypothesis that BBB leakage is responsible for the differences between the HA and LA mouse lines. Although SSIA confirmed BBB differences between both lines, it is not limited to the opioid system and could be a useful model for studying the role of the BBB in molecular communications between the periphery and CNS.
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