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Printable Handouts
Navigable Slide Index
- Introduction
- History of BBB research
- Why study the BBB?
- Drug modifications to enhance BBB uptake
- Drugs and the CNS
- What is the BBB/NVU?
- Comparison of brain and peripheral capillaries
- The NVU in the BBB
- Pericyte endothelial interactions
- Astrocyte endothelial interactions
- Neuronal innervation of the BBB
- Nicotinic receptor subunits at the BBB
- EM of a cerebral capillary (1)
- EM of a cerebral capillary (2)
- BBB tight junction protein interaction
- Endothelial cell tight junctions and transporters
- ZO-1 protein at the tight junction
- CNS diseases associated with BBB dysfunction
- Diseases can yield immune/neuronal responses
- Why study hypoxia/stroke at the BBB endothelia?
- Hypoxia effect on tight junctions
- Biphasic BBB paracellular permeability and edema
- BBB ZO-1 expression post-H/R
- BBB occludin expression post-H/R
- BBB claudin-5 expression post-H/R
- Claudin-5 expression in noninfarcted hemisphere
- Claudin-5 fragmented in early reperfusion injury
- Visualization of BBB "leak"
- Impairment of the BBB in claudin-5 knockout mice
- Effects of hypoxia on BBB tight junctions
- Response of tight junction proteins to stress
- Trafficking and the BBB-occludin
- Stroke, hypertension, and the BBB
- Stroke and the BBB
- Transporters function in edema formation in stroke
- Transporters involved in edema formation at BBB
- Effect of NHE-1 inhibition on brain tissue
- Effect of NHE-1 inhibition on percent total infarct
- Summary of stroke and hypertension
- Diabetes and the BBB
- Diabetes and the BBB (clinical MRI)
- Diabetes and brain fluid volume
- BBB permeability to [C14] sucrose in treated rats
- Lathanum permeability via electron microscopy
- Confocal images of 3 TJ proteins
- Implications of BBB changes in diabetes
- Future diabetes studies
- Summary
- Acknowledgements
Topics Covered
- The blood-brain barrier is not a static barrier
- The blood-brain barrier does inhibit drug delivery to the brain
- The blood-brain barrier is at the level of the endothelial cell cytoarchitecture that line all cerebral blood vessels in the brain
- The blood-brain barrier consists of a unique set of regulated proteins held together in a tight cytoarchitectural matrix to form a tight junction
- Stressors such as head injury, hypoxia, pain and diseases such as M.S, diabetes, Alzheimer's, cancer and stroke alter tight junction proteins of the blood-brain barrier leading to a "leak" and a loss of integrity
- Understanding what controls the integrity of the blood-brain barrier is critical if we are to understand how to treat the diseases of the brain
Talk Citation
Davis, T. (2017, March 27). Blood-brain barrier in health and disease [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 6, 2024, from https://doi.org/10.69645/KRKE2951.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Thomas Davis has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neuroscience
Transcript
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0:00
Hello. My name is Dr. Thomas P. Davis,
I'm a professor of medical pharmacology at
the University of Arizona Medical School in Tucson, Arizona.
The title of this presentation is The Blood Brain Barrier in Health and Disease.
I'd like to first give
0:16
some historical background to blood brain barrier research which started in
1885 with Paul Ehrlich's notation that analine dyes injected
intravenously stained all organs
except the brain and spinal cord as shown in the figure below.
Paul Ehrlich attributed this to an inability of the nervous tissue to take up the dye.
It was in 1900 that Lewandowsky coined the term Bluthirnschranke or
blood-brain-cabinet while studying the penetration
of potassium ferrocyanide into the brain.
It wasn't until 1913, an Ehrlich student,
Edwin Goldman injected water soluble dyes directly into the central nervous system and
showed the classic blood brain barrier separation
between the central nervous system and the rest of the organism.
The question that often comes up
1:05
when individuals want to study the blood brain barrier is why?
What is unique about the blood brain barrier as compared to other barriers in the body?
Well, the first thing that's unique is that the blood brain barrier
provides a problem for drug delivery to the central nervous system.
This has been a serious issue for thousands of years.
The role of the blood brain barrier in a pathophysiology of
central nervous system disease states continues to the present time.
We now know that the brain is no longer immune
privileged and that substances can enter and leave the brain.
However, to get past the blood brain barrier
with a drug or therapeutic has been a serious challenge.
Therefore, understanding the anatomy and cell biology of the Neurovascular unit,
which we now describe the blood brain barrier as part of,
in health and disease is critical for the advancement of
translational research into the clinic.