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.

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 Oxidative Stress and Blood–Brain Barrier Dysfunction Under Particular Consideration of Matrix Metalloproteinases

2011 ◽  
Vol 15 (5) ◽  
pp. 1305-1323 ◽  
Author(s):  
Christine Lehner ◽  
Renate Gehwolf ◽  
Herbert Tempfer ◽  
Istvan Krizbai ◽  
Bernhard Hennig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Matrix Metalloproteinases ◽  
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 Micellar Nanocarriers of Hydroxytyrosol Are Protective against Parkinson’s Related Oxidative Stress in an In Vitro hCMEC/D3-SH-SY5Y Co-Culture System

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 887
Author(s):  
Leah Mursaleen ◽  
Brendon Noble ◽  
Satyanarayana Somavarapu ◽  
Mohammed Gulrez Zariwala
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Culture System ◽  
Iron Chelator ◽  
Brain Barrier ◽  
Neuroprotective Effects ◽  
Blood Brain ◽  
Drug Treatments

Hydroxytyrosol (HT) is a natural phenolic antioxidant which has neuroprotective effects in models of Parkinson’s disease (PD). Due to issues such as rapid metabolism, HT is unlikely to reach the brain at therapeutic concentrations required for a clinical effect. We have previously developed micellar nanocarriers from Pluronic F68® (P68) and dequalinium (DQA) which have suitable characteristics for brain delivery of antioxidants and iron chelators. The aim of this study was to utilise the P68 + DQA nanocarriers for HT alone, or in combination with the iron chelator deferoxamine (DFO), and assess their physical characteristics and ability to pass the blood–brain barrier and protect against rotenone in a cellular hCMEC/D3-SH-SY5Y co-culture system. Both HT and HT + DFO formulations were less than 170 nm in size and demonstrated high encapsulation efficiencies (up to 97%). P68 + DQA nanoformulation enhanced the mean blood–brain barrier (BBB) passage of HT by 50% (p < 0.0001, n = 6). This resulted in increased protection against rotenone induced cytotoxicity and oxidative stress by up to 12% and 9%, respectively, compared to the corresponding free drug treatments (p < 0.01, n = 6). This study demonstrates for the first time the incorporation of HT and HT + DFO into P68 + DQA nanocarriers and successful delivery of these nanocarriers across a BBB model to protect against PD-related oxidative stress. These nanocarriers warrant further investigation to evaluate whether this enhanced neuroprotection is exhibited in in vivo PD models.

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