Distinct patterns of cerebral extravasation by Evans blue and sodium fluorescein in rats.
TLDR
This study suggests that different regions of the brain are equally permeable to LMW inert dyes like the EBD, but are markedly different in permeability to HMW proteins such as EBD-labelled serum albumin.Abstract:
The Evans blue dye (EBD; 961 Da) and the sodium fluorescein dye (NaF; 376 Da) are commonly used inert tracers in blood-brain barrier (BBB) research. They are both highly charged low molecular weight (LMW) tracers with similar lipophobic profiles. Nevertheless, the EBD binds to serum albumin (69,000 Da) to become a high molecular weight (HMW) protein tracer when injected into the circulation, whereas the NaF remains an unbound small molecule in the circulation. In this study, rats were injected with equal doses of either EBD or NaF to monitor their blood and tissue distribution. The EBD was largely confined to the circulation with little accumulation in the peripheral organ and even less accumulation in the central tissue, whereas the NaF distributed more evenly between the blood and the peripheral organ but was also largely excluded from the central tissue. Importantly, the EBD crossed the BBB most effectively at the prefrontal cortex and the cerebellum, and most poorly at the striatum. In marked contrast, the NaF was evenly distributed throughout the brain. Finally, the EBD exhibited this same peculiar tissue distribution profile when administered by either bolus injection or slow infusion. Our study suggests that different regions of the brain are equally permeable to LMW inert dyes like the NaF, but are markedly different in permeability to HMW proteins such as EBD-labelled serum albumin.read more
Citations
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Excitotoxicity and stroke: identifying novel targets for neuroprotection.
TL;DR: This review aims to provide a comprehensive summary of the literature on excitotoxicity and perspectives on how the new generation of excitOToxicity inhibitors may succeed despite the failure of the previous generation of drugs.
Journal ArticleDOI
Markers for blood-brain barrier integrity: how appropriate is Evans blue in the twenty-first century and what are the alternatives?
TL;DR: A combination of different sized, visualizable dextrans and radiolabeled molecules currently seems to be the most appropriate approach for qualitative and quantitative assessment of barrier integrity.
Journal ArticleDOI
Tau depletion prevents progressive blood-brain barrier damage in a mouse model of tauopathy
Laura J. Blair,Haley D Frauen,Bo Zhang,Bryce A. Nordhues,Sara Bijan,Yen-Chi Lin,Frank Zamudio,Lidice D Hernandez,Jonathan J. Sabbagh,Maj-Linda B. Selenica,Chad A. Dickey +10 more
TL;DR: For the first time, data demonstrate that tau alone can initiate breakdown of the blood-brain barrier, but the BBB is remarkably resilient, maintaining its integrity in the face of marked brain atrophy, neuroinflammation and toxic tau accumulation.
Journal ArticleDOI
Optimization of Evans blue quantitation in limited rat tissue samples.
Hwai-Lee Wang,Ted Weita Lai +1 more
TL;DR: The procedure described here used a very small volume (30 µl) per sample replicate, which enabled high-throughput measurements of the EBD concentration based on a standard 96-well plate reader and substantially enhanced the sensitivity of EBD fluorescence spectroscopy.
Journal ArticleDOI
Assessment of Blood-Brain Barrier Disruption in Stroke.
Andrea Kassner,Zamir Merali +1 more
TL;DR: The period during which there is greatest disruption of the BBB coincides with the maximum risk of hemorrhagic transformation, and recombinant tissue-type plasminogen activator (r-tPA) can exacerbate BBB disruption.
References
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Journal ArticleDOI
Fine structural localization of a blood-brain barrier to exogenous peroxidase
TL;DR: These findings localize, at a fine structural level, a "barrier" to the passage of peroxidase at the endothelium of vessels in the cerebral cortex in mice, particularly with reference to a recent study in which similar techniques were applied to capillaries in heart and skeletal muscle.
Journal ArticleDOI
Junctions between intimately apposed cell membranes in the vertebrate brain
TL;DR: Endothelial and epithelial tight junctions occlude the interspaces between blood and parenchyma or cerebral ventricles, thereby constituting a structural basis for the blood-brain and blood-cerebrospinal fluid barriers.
Journal ArticleDOI
Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders.
TL;DR: Mechanisms of BBB dysfunction in neurodegenerative disorders, notably Alzheimer's disease, are examined, and therapeutic opportunities relating to these neurovascular deficits are highlighted.
Journal ArticleDOI
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Robert D. Bell,Ethan A. Winkler,Itender Singh,Abhay P. Sagare,Rashid Deane,Zhenhua Wu,David M. Holtzman,Christer Betsholtz,Annika Armulik,Annika Armulik,Jan Sallstrom,Bradford C. Berk,Berislav V. Zlokovic,Berislav V. Zlokovic +13 more
TL;DR: It is shown that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes, which suggest that CypA is a key target for treating APoe4-mediated neurovascular injury and the resulting neuronal Dysfunction and degeneration.
Journal ArticleDOI
The blood-brain barrier in brain homeostasis and neurological diseases.
Nicolas Weiss,Florence Miller,Florence Miller,Sylvie Cazaubon,Sylvie Cazaubon,Pierre-Olivier Couraud,Pierre-Olivier Couraud +6 more
TL;DR: This review will focus on the implication of brain endothelial tight junctions in BBB architecture and physiology, will discuss the consequences of BBB dysfunction in these CNS diseases and will present some therapeutic strategies for drug delivery to the brain across the BBB.
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