BBB: Misunderstood Key To Finding Life Saving Cures

18 Dec 2007
http://www.medicalnewstoday.com/articles/92046.php

An international team of scientists that includes a Saint Louis University researcher suggest several strategies to propel research for treatments of brain diseases that include multiple sclerosis, Alzheimer's disease, obesity and stroke in the January issue of the Lancet Neurology.

Their review article, which focuses on surmounting obstacles posed by the blood-brain barrier (BBB), is available in an early online edition of the prestigious medical journal on Dec. 17.

The blood-brain barrier is a gate-keeping system of cells that protects the brain from toxins and lets in nutrients. Because it passes no judgment on which foreign substances are there to treat diseases and which are penetrating the brain to do harm, it locks all of them out. That makes getting drugs into the brain where they can do their work in treating brain diseases difficult.

"A big part of our work is raising the awareness about the blood-brain barrier as an intimate part of the disease process," said William A. Banks, M.D., professor of geriatrics and pharmacological and physiological science at Saint Louis University School of Medicine, and a member of the research team.

"You can't get drugs into the brain or understand brain disease without understanding the blood-brain barrier, which is among our most significant recommendations for future research."

The blood-brain barrier is woefully misunderstood, said Banks, who also is a staff physician at Veterans Affairs Medical Center in St. Louis.

"The general theme of our review article is the blood-brain barrier is not a brick wall but a regulating interface between the brain and the rest of the body. Look at the brain as an island, where all raw materials have to be imported. The blood-brain barrier is the shipping and communications system that connects the island (the brain) to the rest of the world (the body)."

Sometimes the blood-brain barrier lets in things that it shouldn't and doesn't let out things that it should. Learning more about the secrets of the blood-brain barrier system is critical in understanding Alzheimer's disease, for instance, because the BBB makes it difficult to target medication where it's needed in the brain and won't allow toxic amyloid beta proteins, believed to cause Alzheimer's, to drain out of the brain.

Much of Banks' work focuses on the function of the blood-brain barrier in regulating the immune system, the body's natural defense in fighting disease. The cells that make up the blood-brain barrier help the brain and immune system communicate, he explained.

The crash of that communication system can impact diseases including Alzheimer's disease, stroke and multiple sclerosis. In the Lancet Neurology article, Banks and his colleagues called for more research to better understand how the blood-brain barrier relates to immune cells.

The article also recommended wider use of state-of-the-art imaging to examine how the blood-brain barrier and the rest of central nervous system interact, particularly in patients who have spinal cord injuries, head trauma and stroke. Changes to the blood-brain barrier could give important clues about injuries to the central nervous system and the growth of tumors.

The review also called for investigators from various disciplines and who work in different institutions and laboratories to collaborate on blood-brain barrier research to take research from an animal model to patient clinical trials.

An international committee of 14 scientists who specialize in blood-brain barrier research wrote the review article. In addition to SLU and the VA, participating institutions included Oregon Health & Science University, King's College, Memorial Sloan-Kettering Cancer Center, University of Manitoba, University of Arizona, University of Bern, Texas Tech University Health Sciences Center, University of Rochester, University of California Los Angeles, University of New Mexico and University of Minnesota Medical School.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

Saint Louis University Medical Center
St. Louis, MO 63103
United States
Saint Louis University Medical Center

Is this new? Is it connected or supportive to your work?

Sounds like you could have written that....

Hoping for answered questions - the patient comm has spent so much time researching and wanting the latest confirmation about it

Cheers!
paula

Hi Paula,
It is good to hear from you again. It supports the argument that the BBB is not accorded the status it deserves in research. "The blood-brain barrier is woefully misunderstood, said Banks". How right he is, and even most of the research on the BBB is spent trying to open the gates to let large drugs in, when this can only exacerbate our symptoms by letting more toxins in, while it is temporarily open. What we need is a simple and convenient treatment to maintain the BBB at the level of permeability of a healthy blood-brain barrier.
I am amazed the medical profession seems to state black or white, a substance either can cross the BBB or it doesn't. What they mean, is that relates to a healthy BBB with a standard permeabilty. It is like quoting amps without volts, or a boiling point without the pressure it is measured at. However, 5 million of the world population have defective BBB's and to give a go, no go decision on a substance does not apply to us. Remember the Gulf War Syndrome, where they gave troops drugs to combat chemical weapons. They confidently said, that these drugs would not cause any neurological problems since they did not pass the BBB. Surprise, the stress of battle opened the BBB and they found substantial amounts of the drug in the brain. See
http://www.sciencenews.org/pages/pdf...4/15024-10.pdf
The article is getting on the right track when it says,
" Sometimes the blood-brain barrier lets in things that it shouldn't and doesn't let out things that it should". However, they should add,
"Sometimes it lets things out that that it shouldn't", like our tiny reserve of dopamine gets dumped to the bloodstream in times of stress, and we freeze on the spot. But they are starting to understand that the BBB can be manipulated wider or narrower, and that is a step forward.
I get hope when I see them say,
""A big part of our work is raising the awareness about the blood-brain barrier as an intimate part of the disease process,"
and
"The review also called for investigators from various disciplines and who work in different institutions and laboratories to collaborate on blood-brain barrier research "
However, now into my 70's, how much longer can I afford to wait until they lumber into action, and spend money on research in the right area.
Ron

Here is another paper being published early in 2008 on the BBB in PD. I have been in touch with one of the authors, some 9 months ago, and gave the information in my thread, "BBB updated". The interesting point is if we can manipulate the BBB to a porosity of a healthy personm we could open the door to stopping PD, AD, MS, ALS and others in one.
Lancet Neurol 2008; 7: 84–96
Strategies to advance translational research into brain
barriers.
Edward Neuwelt, N Joan Abbott, Lauren Abrey, William A Banks, Brian Blakley, Thomas Davis, Britta Engelhardt, Paula Grammas,
Maiken Nedergaard, John Nutt, William Pardridge, Gary A Rosenberg, Quentin Smith, Lester R Drewes

"In the clinical arena of neurodegenerative disorders,
the BBB is traditionally seen as irrelevant or simply as a
barrier to treatment. In reality, the brain barriers have
important roles in the pathology and progression of a
broad spectrum of CNS disorders, including Alzheimer’s
disease, Parkinson’s disease, amyotrophic lateral
sclerosis, and multiple sclerosis. From a clinical and
basic science perspective, the brain barriers are vital for
CNS homoeostasis and the preservation of neuronal
integrity. The alterations to the cerebral microcirculation
and BBB in neurodegenerative diseases need to be
investigated, and the CNS microvasculature might be a
new target for therapeutic development."

Discussion with another researcher gave me an answer I have been seeking for some time, so another question and answer can be added to the list in my BBB update thread. The BBB is involved in AD as well as PD, but what decides which disease you get? If the BBB was defective uniformly, you might expect we would get both diseases. I speculated AD might require say, a higher permeability than PD, OK, but that would mean you get PD then get AD. That didn't add up. However, I now learn that the BBB is in sections, protecting various areas, So presumably you could be born with the pD section defective, or could damage it environmentally, eg pesticides, and just get PD not AD. Or in rare cases you could damage both ares and get both diseases. It is increasingly looking as though Rick is right when he suggests inflammation precedes the BBB damage.

Ron