Blood-brain barrier dysfunction in parkinsonian midbrain in vivo

2005 ◽  
Vol 57 (2) ◽  
pp. 176-179 ◽  
Author(s):  
Rudie Kortekaas ◽  
Klaus L. Leenders ◽  
Joost C. H. van Oostrom ◽  
Willem Vaalburg ◽  
Joost Bart ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain

scholarly journals Myeloperoxidase-Derived Oxidants Induce Blood-Brain Barrier Dysfunction In Vitro and In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e64034 ◽  
Author(s):  
Andreas Üllen ◽  
Evelin Singewald ◽  
Viktoria Konya ◽  
Günter Fauler ◽  
Helga Reicher ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain

scholarly journals Effects of Bradykinin on Permeability and Diameter of Pial Vessels In vivo

1984 ◽  
Vol 4 (4) ◽  
pp. 574-585 ◽  
Author(s):  
Andreas Unterberg ◽  
Michael Wahl ◽  
Alexander Baethmann
Keyword(s):  
Blood Brain Barrier ◽  
Topical Administration ◽  
Vessel Diameter ◽  
Brain Barrier ◽  
Maximal Response ◽  
Barrier Dysfunction ◽  
Kinin System ◽  
Pial Vessels ◽  
Blood Brain

The effect of bradykinin on the permeability and vasomotor response of pial vessels has been studied to enhance our understanding of the pathophysiological role of the kallikrein–kinin system in cerebral tissue. Intravital fluorescence microscopy of the pia arachnoidea was conducted using Na+-fluorescein, FITC-dextran, and FITC-albumin as low and high molecular weight blood–brain barrier indicators. Massive arterial dilatation evolved immediately upon administration of bradykinin by superfusion of the exposed cerebral surface. An increase of the arterial diameter by 40% was the maximal response found at bradykinin concentrations of 4 × 10−5 M. Arterial dilatation became attenuated with continuous superfusion of the preparation with bradykinin. In pial veins, a moderate reduction of the vessel diameter was observed, however, only after prolonged superfusion of the preparation. Bradykinin led to selective opening of the blood–brain barrier for Na+-fluorescein at super-fusate concentrations of ⩾4 × 10−7 M, but not for FITC-dextran or FITC-albumin. Topical administration of l-isoproterenol (10−4 M) was found to prevent extravasation of Na+-fluorescein in the presence of bradykinin concentrations of 4 × 10−6 M. Protection of the blood–brain barrier by isoproterenol was not observed when higher concentrations of bradykinin were employed. Intracarotid infusion of bradykinin led also to a selective opening of the blood–brain barrier for Na+-fluorescein, but not for FITC-dextran or FITC-albumin. In contrast to superfusion, this route of administration did not induce changes of the vasomotor behavior of the arteries or veins. Additional experiments with B1-agonists and -antagonists suggest that bradykinin causes the opening of the blood–brain barrier through an interaction with B2-receptors on endothelial cells, and arterial dilatation via interaction with B2-receptors on vascular smooth muscle cells. Our findings support the concept that the release of kinins in the brain during an acute cerebral lesion mediates secondary damaging processes by the enhancement of blood–brain barrier dysfunction.

scholarly journals Contribution of thrombin-reactive brain pericytes to blood-brain barrier dysfunction in an in vivo mouse model of obesity-associated diabetes and an in vitro rat model

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0177447 ◽  
Author(s):  
Takashi Machida ◽  
Fuyuko Takata ◽  
Junichi Matsumoto ◽  
Tomoyuki Miyamura ◽  
Ryosuke Hirata ◽  
...  
Keyword(s):  
Mouse Model ◽  
Blood Brain Barrier ◽  
Rat Model ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
Brain Pericytes

scholarly journals Hemoglobin-Induced Oxidative Stress Contributes to Matrix Metalloproteinase Activation and Blood–Brain Barrier Dysfunction in vivo

2010 ◽  
Vol 30 (12) ◽  
pp. 1939-1950 ◽  
Author(s):  
Masataka Katsu ◽  
Kuniyasu Niizuma ◽  
Hideyuki Yoshioka ◽  
Nobuya Okami ◽  
Hiroyuki Sakata ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Apoptotic Cell ◽  
Brain Barrier ◽  
Intracerebral Injection ◽  
Barrier Dysfunction ◽  
Mmp Inhibitor ◽  
Blood Brain ◽  
Albumin Leakage

Hemoglobin (Hb) released from extravasated erythrocytes is implicated in brain edema after intracerebral hemorrhage (ICH). Hemoglobin is a major component of blood and a potent mediator of oxidative stress after ICH. Oxidative stress and matrix metalloproteinases (MMPs) are associated with blood–brain barrier (BBB) dysfunction. This study was designed to elucidate whether Hb-induced oxidative stress contributes to MMP-9 activation and BBB dysfunction in vivo. An intracerebral injection of Hb into rat striata induced increased hydroethidine (HEt) signals in parallel with MMP-9 levels. In situ gelatinolytic activity colocalized with oxidized HEt signals in vessel walls, accompanied by immunoglobulin G leakage and a decrease in immunoactivity of endothelial barrier antigen, a marker of endothelial integrity. Administration of a nonselective MMP inhibitor prevented MMP-9 levels and albumin leakage in injured striata. Moreover, reduction in oxidative stress by copper/zinc-superoxide dismutase (SOD1) overexpression reduced oxidative stress, MMP-9 levels, albumin leakage, and subsequent apoptosis compared with wild-type littermates. We speculate that Hb-induced oxidative stress may contribute to early BBB dysfunction and subsequent apoptosis, partly through MMP activation, and that SOD1 overexpression may reduce Hb-induced oxidative stress, BBB dysfunction, and apoptotic cell death.

scholarly journals 3D hydrogel models of the neurovascular unit to investigate blood-brain barrier dysfunction

2021 ◽  
Author(s):  
Geoffrey Potjewyd ◽  
Katherine Kellett ◽  
Nigel M Hooper
Keyword(s):  
Blood Brain Barrier ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Brain Parenchyma ◽  
Physical Models ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain

The neurovascular unit (NVU), consisting of neurons, glial cells, vascular cells (endothelial cells, pericytes and vascular smooth muscle cells) together with the surrounding extracellular matrix (ECM), is an important interface between the peripheral blood and the brain parenchyma. Disruption of the NVU impacts on blood-brain barrier (BBB) regulation and underlies the development and pathology of multiple neurological disorders, including stroke and Alzheimer’s disease. The ability to differentiate induced pluripotent stem cells (iPSCs) to the different cell types of the NVU and incorporate them into physical models provides a reverse engineering approach to generate human NVU models to study BBB function. To recapitulate the in vivo situation such NVU models must also incorporate the ECM to provide a 3D environment with appropriate mechanical and biochemical cues for the cells of the NVU. In this review we provide an overview of the cells of the NVU and the surrounding ECM, before discussing the characteristics (stiffness, functionality and porosity) required of hydrogels to mimic the ECM when incorporated into in vitro NVU models. We summarise the approaches available to measure BBB functionality and present the techniques in use to develop robust and translatable models of the NVU, including transwell models, hydrogel models, 3D-bioprinting, microfluidic models and organoids. The incorporation of iPSCs either without or with disease-specific genetic mutations into these NVU models provides a platform in which to study normal and disease mechanisms, test BBB permeability to drugs, screen for new therapeutic targets and drugs, or to design cell-based therapies.

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