Cross-or-Not the Blood-Brain Barrier?

The Martial Art of Wellness

Volume 17 – January 2018

(Archive of Previous BioNews)

DEAR FRIENDS

QUOTE OF THE MONTH

” If you can increase brain health, the rest of the body is a no-brainer. “

– Michael Kiriac, PhD

THIS ISSUE’S TESTIMONIAL: The trembling in her voice went away!

“ Hi,  I wanted to let you know about the great results my mother is having with the BAC F3. She is 84 and her voice has been trembling for a few years now, her head bobbing and she was starting to get very confused or angry about things she used to know how to do. She started taking one pill a day of F3 and stopped because she told me “they are very strong!” … a little more probing and I realized she was getting detox diarrhea from it. So upon your suggestion, I opened the capsules and prepared a 14 days supply of 1/2 capsule of F3 for her to take. She started taking those and continued on (with a little fear on her part) to taking a full capsule a day. Low and behold, the trembling in her voice went away! She is also in an overall better mood and is not getting confused anymore. I have had to explain to her that she is still way below the recommended minimum dosage and that it would be a good idea to increase the dosage. It’s been a slow process of lots of hints, suggestions and explanations so that she would understand why it would be a good idea! She is now realizing that she just might get her head shaking to stop (she doesn’t like to be like an old lady), have more energy and vitality, loose weight… I’ve had to explain to her that if you don’t change the oil in a car, it will soon stop running. Since we both know she won’t do any cleanses, taking the F3 pills is the next best option as it helps her body detoxify. I am finally getting through to her and now her latest was that she didn’t want to use to many for fear of running out… so I just bought a year’s supply! Beides, I wouldn’t want to run out myself, as I’ve had a lifelong history of depression, despite all the diet changes and emotional work I’ve done on myself. Depression and bipolar affect pretty much every member of my family. Taking the F3 is an easy way to feed my brain directly and keep it functioning. Thank you for a great product! With much love and gratitude,”

– Tamara, New York, NY

THE MARTIAL ART OF WELLNESS (Cross-or-Not the Blood-Brain Barrier)

Hopefully, most of you reading this article have already read that Bio-Algae Concentrates (BAC) cross the blood-brain barrier (BBB) nourishing cells that make up the hypothalamus, and “Awaken the Genius Within.” If not, then I invite you to read all about Dr. Michael Kiriac, Ph.D.’s research at www.awakeningthegeniuswithin.com.  Evolved over 3.8 billion years from cyanobacteria, the first unicellular cell, humans are the most biochemically complex being.  Unlike any other species, humans can sing at the piano, while at the same time be planning tomorrow’s wedding.  And amongst all our metabolic functions, likely the most sophisticated is this survival business of crossing-or-not the BBB.

The Blood-Brain Barrier

Click image for a simple description

The blood-brain barrier (BBB) is a physical barrier that prevents entry of large and potentially toxic molecules into the brain, thus separating the central nervous system and systemic circulation. It is formed by tight junctions between brain endothelial cells, which selectively prevent the diffusion of hydrophilic molecules and pathogens such as bacteria from entering the brain parenchyma. As well as protecting the brain from potentially damaging molecules and plasma fluctuations, the BBB also serves a homeostatic purpose, supplying the brain with nutrients (via selective transporters) and aiding removal of waste products. By maintaining a stable environment, the blood-brain barrier helps ensure synaptic transmission.

Not all foods are created equal

Thus, when it comes time to cross the BBB, not all foods are created equal, and ounce-for-ounce, when compared with other foods, supplements, or medications, Bio-Algae Concentrates (BAC) is likely the most efficient at crossing the BBB and nourishing cells of the mission-critical hypothalamus.  In the words of Michael Kiriac, Ph.D.,

“The culmination in cellular nutrition is the science of selecting and combining foods with highest efficiency at nourishing the cells of the hypothalamus, our mission-critical brain organ that regulates homeostasis, allowing for ideal endocrine and organ balance”

BAC’s nutrients, capable of efficiently crossing the BBB, reaching the hypothalamic region and, delivering the perfect meal, the complete and balanced set of amino acids, fats, minerals, trace elements, a bounty of pigments like chlorophylls and carotenoids, rare phytonutrients, many of which are unavailable in our regular foods. Each meal of BAC, even as small as one capsule, is sufficient to cause this natural food-derived energetic awakening of the hypothalamus.

Get to know the BBB

Next, in order to increase your understanding of the BBB, this incredibly sophisticated survival metabolism our body is equipped with, I am sharing an essay written by my daughter Maryse Thomas.

This essay is the mock posthumous nomination of neurophysiologist Lina Stern for the Nobel Prize in Physiology or Medicine, in recognition of her work illuminating the existence and function of the blood-brain barrier. – By Maryse Thomas March 2017.

The blood-brain barrier refers to a diffusion barrier formed by the endothelial walls of the blood vessels and capillaries in the brain. This barrier prevents most substances in the blood from entering the brain while allowing small lipophilic molecules like O2 and CO2 to diffuse freely (1). Nutrients or large molecules required for brain function, such as glucose, amino acids, and insulin, enter the brain via transporters or receptor-mediated endocytosis (1). Today it is known that the blood-brain barrier serves three main functions, which are the protection of the brain from the blood milieu, selective transport of molecules, and metabolism or modification of blood- or brain-borne substances (2). The blood-brain barrier is of interest to the field of medicine because barrier dysfunction can initiate or contribute to neurological diseases and the barrier presents a major obstacle for drug delivery to the brain (3). Each year, the Nobel Prize in Physiology or Medicine is awarded to a discovery that has changed our understanding of the life sciences or the practice of medicine. This year, I would like to posthumously nominate neurophysiologist Lina Stern for her work illuminating the existence and function of the blood-brain barrier, which has not previously been recognized by the Nobel Committee. The Committee faces two challenges when awarding a Nobel Prize. These are choosing a discovery worthy of acknowledgment and selecting a maximum of three awardees to attribute it to. I argue that the discovery of the blood-brain barrier is worthy of a Nobel Prize and one that should rightly be ascribed to Stern.

HISTORY OF THE BLOOD-BRAIN BARRIER

While the discovery of the blood-brain barrier has historically been credited to multiple individuals, a closer examination of the literature reveals the important contributions that Stern made to this effect. The barrier’s discovery began with a series of observations on how substances are taken up by the nervous system of injected animals. Paul Ehrlich, of Nobel Prize fame, is usually credited with making the first observation in 1885 that trypan blue dye injected into the bloodstream stains all organs of the body except for the brain and spinal cord (4).

The blood-brain barrier in the developing brain. A. A guinea pig embryo injected with trypan blue in a 1920 experiment by Wislocki. Every organ in the body is stained apart from the brain and spinal cord. B. A pig embryo injected with sodium ferrocyanide in the spinal canal and treated with Prussian blue by Weed in 1917. Staining is confined to the CSF with some diffusion into the brainstem and midbrain. (Reproduced from Saunders et al., 2014).

However, he attributed this lack of staining to the brain having a low affinity for the acidic dye and not to any special property of the blood vessels (2,5,6). Between 1898 and 1900, German scientists Biedel, Kraus, and Lewandowsky reported that intravenous injections of toxic substances did not produce pharmacological effects, presumably because of a barrier – which Lewandowsky is said to have called blut-hirn-schranke (blood-brain barrier) (2) – that prevented them from reaching the brain (5,7). However, no assessment of the concentration of these substances in the brain was made. In 1909 and 1913, Ehrlich’s student, Edwin Goldmann, completed two experiments in which he first showed that trypan blue injected systemically is taken up by the body tissues, meninges, and choroid plexus but not the brain or cerebrospinal fluid (CSF), and second that dye injected into the CSF was taken up by the brain and CSF only (6,7).

Goldmann’s trypan blue injection experiments. A. From Goldmann’s “first experiment,” an adult rat that has been injected systemically with trypan blue solution. B. From Goldmann’s “second experiment,” the brain and spinal cord of an adult rat injected with trypan blue in the lumbar spinal canal. (Reproduced from Saunders et al., 2014).

While these studies clearly demonstrated a compartmentalization between brain/CSF and body, Goldmann incorrectly proposed that the choroid plexus must be the port of entry for nutrients to enter the brain (2,5). This view was referred to as the “die Weg über den Liquor” or “way of the spinal fluid” concept (2,5). Lina Stern, who was from the USSR but was working at the University of Geneva in Switzerland, entered the scene in 1918 and published a series of systematic experiments on the movement of various substances from the blood into the nervous system with Gautier (5,6). In these studies, the two used chemical methods to estimate the amount of solutes that were able to permeate the brain and CSF. From these studies they concluded that there exists a barrier between blood and brain, which they termed “barrière hématoencéphalique” as well as a barrier between blood and CSF (2,4). In an influential 1956 review (5), however, English physiologist Hugh Davson wrote that Stern and Gautier believed in the “way of the spinal fluid” theory as well as the notion that the blood-brain barrier was an absolute barrier to all substances. He dismissed these ideas as “intellectually inadequate” and paid no service to any of Stern’s later articles. In a recent publication, Saunders and colleagues (4) performed a careful review of the original blood-brain barrier studies in their native languages and argued that Stern’s contribution to blood-brain barrier history has been overlooked. In their survey, they found that Lewandowsky did not actually use the term blut-hirn-schranke in any of his publications, so Stern and Gautier were the first to name the blood-brain barrier. When authors preceding Stern including Ehrlich and Goldmann noted an absence of dye staining in the brain, they either did not speculate a reason or attributed it to something other than a protective function of the blood vessels. Stern, on the other hand, expressly assigned a role to the blood-brain barrier in impeding substance flow into the brain. Furthermore, Davson’s criticisms regarding Stern’s views were undeserved since she had clearly stated her belief in a route for substances to reach the brain directly through the blood and was apparently misquoted by Davson or earlier authors. Finally, she did not believe in the absoluteness of the blood-brain barrier and had, in a 1934 review paper, independently introduced the notions of barrier selectivity and barrier resistance, arguing that the barrier both selectively allows certain substances to enter the brain and protects the internal milieu of the brain from that of the blood. According to Saunders et al., this view of the blood-brain barrier controlling the internal environment of the brain was a “major physiological concept that was decades ahead of its time.” If we are to accept the authors’ conclusions, then Stern was the first to originate the modern concept of the blood-brain barrier and the majority of her contributions to its research were not adequately recognized by history.

IMPACT OF THE BLOOD-BRAIN BARRIER DISCOVERY

Today, knowledge of the blood-brain barrier is essential to the practices of medicine, neurology, and neuroscience. The studies of Lina Stern helped establish the relationship between blood, brain, and CSF, whose normal function are important for brain health. Knowledge of the blood-brain barrier is also critical for the development of neurotherapeutic drugs as this protective barrier excludes 98% of the small-molecule and 100% of the large-molecule drugs currently in existence (8,9). Clearly, this presents a major challenge for the treatment of nervous system disorders. Stern’s research helped underline the fact that the barrier’s action is not uniform with respect to all blood-borne substances. This knowledge has been used to develop drugs such as L-DOPA, the precursor of dopamine, which is small enough to cross the blood-brain barrier while dopamine is not and is an effective treatment for Parkinson’s disease (8). The future of barrier research will be to better understand its endogenous transport systems in order to engineer drugs that can cross it using transport mechanisms (9).

CONCLUSION

The blood-brain barrier is a vital component of nervous system function and health. Almost all of our knowledge of this barrier comes from research undertaken in the last century and admittedly, most of it does not come from Stern. While Stern performed careful, thorough, and insightful studies of the blood-brain and the blood-CSF barriers, the majority of her work appears to have gone unnoticed or misquoted by twentieth-century researchers. This had the effect of obscuring Stern’s important contribution from history and slowing down progress in blood-brain barrier research for decades. Yet, it is apparent that Stern identified the existence of and postulated the function of the blood-brain barrier before anyone else, making her deserving of the Nobel Prize for its discovery. In discussing Stern’s achievements, it is also worth pointing out that she had to overcome numerous social and political barriers in order to pursue her research. It is impossible to do justice to Stern’s life story here, so I will point the reader to the biography written by Vein (10). However, I will mention that when Stern began her career, she was one of very few female academics in all of Europe and the USSR. Furthermore, following World War II, Stern was submitted to trials including imprisonment, exile, and the execution of her close contemporaries because of her position as an influential Jewish scientist in Soviet Russia (10). While the Nobel Prize is not awarded for lifetime achievement or scientific leadership, Stern happens to also excel in these categories and is a notable role model for female and minority group scientists. The Nobel Committee has the opportunity to recognize Lina Stern and set the historical record straight by posthumously awarding her the 2017 Nobel Prize in Physiology or Medicine for her work illuminating the existence and function of the blood-brain barrier.

WORKS CITED

1. Ballabh, P., Braun, A., & Nedergaard, M. (2004). The Blood-Brain Barrier: An Overview. Structure, Regulation, and Clinical Implications. Neurobiology of Disease, 16, 1–13.
2. Ribatti, D., Nico, B., Crivellato, E., & Artico, M. (2006). Development of the Blood-Brain Barrier: A Historical Point of View. The Anatomical Record, 289(B), 3–8.
3. Zlokovic, B. V. (2008). The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders. Neuron, 57, 178–201.
4. Saunders, N. R., Dreifuss, J.-J., Dziegielewska, K. M., Johansson, P. A., Habgood, M. D., Møllgård, K., & Bauer, H.-C. (2014). The Rights and Wrongs of Blood-Brain Barrier Permeability Studies: A Walk Through 100 Years of History. Frontiers in Neuroscience, 8, 1–26.
5. Davson, H. (1989). History of the Blood-Brain Barrier Concept. In E. A. Neuwelt (Ed.), Implications of the Blood-Brain Barrier and Its Manipulation (1st ed., pp. 27–52). New York: Plenum Publishing Corporation.
6. Davson, H. (1976). The Blood-Brain Barrier. Journal of Physiology, 255, 1–28.
7. Bradbury, M. (1993). The Blood-Brain Barrier. Experimental Physiology, 78, 453– 472.
8. Pardridge, W. M. (2005). The Blood-Brain Barrier: Bottleneck in Brain Drug Development. The Journal of the American Society for Experimental NeuroTherapeutics, 2, 3–14.
9. Pardridge, W. M. (2012). Drug Transport Across the Blood-Brain Barrier. Journal of Cerebral Blood Flow and Metabolism, 32, 1959–1972.
10. Vein, A. A. (2008). Science and Fate: Lina Stern (1878-1968), a Neurophysiologist and Biochemist. Journal of the History of the Neurosciences, 17(2), 195–206.

Awakening the Genius Within

In ending, please refer to a set of charts that I have created to illustrate the mechanism of action and biochemical rationale to shed light on why BAC crosses the BBB. Click on the title image to view the charts.

Click on the image to view the charts