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Blood Brain Barrier Deficiency

What is the Blood-Brain Barrier?

The blood-brain barrier (BBB) is the specialized system of capillary endothelial cells that protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. Unlike peripheral capillaries that allow relatively free exchange of substance across / between cells, the BBB strictly limits transport into the brain through both physical (tight junctions) and metabolic (enzymes) barriers. Thus the BBB is often the rate-limiting factor in determining permeation of therapeutic drugs into the brain. Additionally, BBB breakdown is theorized to be a key component in central nervous system (CNS) associated pathologies. BBB investigation is an ever growing and dynamic field studied by pharmacologists, neuroscientists, pathologists, physiologists, and clinical practitioners.

This information is presented as a potential solution to many perplexing problems associated with MS, in the hope that a qualified research organization may choose to follow up on the ideas. Some possible courses of treatment are suggested. These suggestions are made for the benefit of those in qualified research positions to consider. They are not intended for self-treatment by individuals. An individual may want to discuss these ideas with his personal physician if it seems appropriate. The ideas presented here may turn out to be important in the understanding and treatment of MS or they may turn out to be another false diversion. Only time will tell.

Introduction

Multiple sclerosis (MS) is a disease in which a person's immune system attacks his own central nervous system. Most of the observed behavior of MS has not made sense. However, recently it has been observed that during an attack there is evidence that a person's blood-brain barrier, a component of his circulatory system, is not working properly. If one models the disease as one which is controlled by the integrity of the blood-brain barrier, then most of the puzzling aspects of the disease disappear, having rational explanations.

Furthermore, if MS attacks occur as a result of a weakened, malfunctioning blood-brain barrier, then an obvious treatment is suggested: strengthen the barrier.

Nutrition and herbs play a major role in blood-brain barrier integrity. Blueberries and garlic each have the potential to affect certain potential causes of blood-brain barrier deficiency.

A Review of Multiple Sclerosis

Multiple Sclerosis (MS) is a disease in which certain types of white blood cells called T lymphocytes attack a fatty covering found in the central nervous system. More specifically, most of the individual nerve cells of the brain and spinal chord, which make up the central nervous system, are surrounded by a covering called the myelin sheath. The myelin sheath helps insulate signals from adjacent nerves and increase the speed of signal transmission along the nerve. It is the myelin sheath which is attacked by the lymphocytes. During an attack the lymphocytes destroy the myelin, first causing inflammation followed by the formation of scar tissue.

Normally, lymphocytes do not attack a person's own body. Rather, they are programmed to distinguish between a person's body and foreign, invading substances. Their purpose is to protect the body from invading bacteria and viruses. Occasionally, though, they can develop sensitivity against a person's own cells. This is called an autoimmune disease. Rheumatoid arthritis and lupus are examples of two other autoimmune diseases.

One of the more puzzling aspects of MS is its inconsistency. The attacks typically occur at localized, random sites on a periodic basis. This is opposed to a generalized, continuous attack. Between episodes, a person will typically recover much of the lost function from the attack. The period of time between episodes also varies from individual to individual. Some people have a very slow progress and may not be adversely handicapped decades later and others will have a very rapid progress, culminating in their death within a few years. Within the widespread personal variation, however, is an overall tendency for subsequent attacks to be worse than the first, so that the disease, over time, does tend to worsen. The only thing definite about the disease is its indefiniteness; a person's past history with the disease is not necessarily an indicator of his future history.

Whenever a specific nerve is attacked, the nerve pulses passing through the region of attack tend to weaken and slow down. During remission, that is, the period between attacks, there is typically a certain amount of recovery of the nerve's functionality. Apparently, though, once a site has been attacked it is more likely to be the site of future attacks. Eventually, the scar tissue formed can be so problematic that a nerve cell may die. This, of course, leads to a permanent loss of functionality.

Typical symptoms of MS include sensory problems and muscle control problems, depending on the function of the specific nerve under attack. Thus, a person may feel a numbness or tingling in an arm or leg, or the limb may feel heavy and unresponsive, or any number of other symptoms that could be caused by a nerve not functioning properly.

Short of an autopsy to examine one's brain or spinal chord, so that the scars may be directly observed, there is no specific, definitive test for the disease. Autopsy is an extreme form of diagnosis for those still alive. However, recent advances with magneto-resonance imaging (MRI) scans have shown the scars at the attack sites typically produce characteristic shadows on the scans. These shadows, when coupled with the observed symptoms of MS, tend to be fairly reliable indicators of the disease.

Initially, it was felt that MS was caused by a virus. This was based primarily upon statistical analyses of the medical history of MS patients, who invariably seemed to have had an earlier exposure to a disease such as measles or mumps. However, identification of a virus has eluded many researchers for a long period of time.

Lately, MS is seen as being a disease of the immune system. The cause of the inflammation leading to the depletion of the myelin and the forming of scar tissue has been traced to T4 lymphocytes, certain white blood cells in a person's blood stream.

These two viewpoints are not mutually contradictory. Thus, a person may suffer from a viral infection which somehow sensitizes the immune system to attack myelin. The concept that MS is primarily caused by immune system malfunctions does not explain adequately many observations concerning the disease. For instance, if the disease is primarily caused by an immune system malfunction, why is its behavior so random? One would expect a continuous, universal attack if the nervous system were the sole influence.

Another puzzling phenomenom is that autopsies of the general population have revealed that perhaps as much as two-percent of the population has MS scars in their central nervous system. This is perhaps twenty times larger than one would expect. In general, those who had the scars but did not have any observed symptoms also had very few scars. To me, though, the significant thing is that in order to get any scars at all, these people needed to have an immune system with lymphocytes sensitized to their own myelin. Yet, in these cases, the disease did not seem to progress very rapidly at all. Why?

The Blood-Brain Barrier (BBB)
Actually, it should be irrelevant whether or not a person's lymphocytes have been sensitized to his myelin. Normally, the white blood cells do not have access to the nerve cells of the brain or the spinal chord. There is a natural wall separating the two systems from each other; this wall is called the blood-brain barrier (BBB). The BBB is actually a feature of the capillaries found in the central nervous system.

Capillaries are very tiny blood vessels. Nutrients flow out of the capillaries into the surrounding tissues and waste products are picked up by the capillaries for removal from the tissues. The capillaries are themselves made up of tiny cells. In most of the body these cells are very loosely connected, with large gaps extending between cell walls. These gaps allow large materials to flow in and out of the capillaries, including white blood cells. However, in the brain and spinal chord, the capillary structure is different. The walls of adjacent capillary cells are very tightly cemented to each other and only very tiny gaps exist. These gaps are so small that even large protein molecules cannot pass through them. Normally, the white blood cells would not be able to go through the gap.

Recent studies have shown a breakdown in the blood-brain barrier of people having an attack of multiple sclerosis. The articles I have seen merely report the breakdown of the BBB as an observed fact; no conclusions are drawn from it.

However, all of a sudden, our whole perspective changes. Suppose that MS is NOT primarily an immune system problem, but rather a blood-brain barrier problem. If this is the case, all of a sudden lots of things begin to make sense.

Assume that in most people the blood-brain barrier functions as it is supposed to. Let's further suppose that it is even common for a person with an attack of measles to end up with lymphocytes sensitized to myelin. With a normal BBB, the sensitized lymphocytes do not have access to the nerve cells and there is no MS. Sensitized lymphocytes are then not the real problem.

However, let's suppose that some people with sensitized lymphocytes also have a weakened blood-brain barrier. Then, depending on the extent of the weakness, these people will have varying degrees of MS symptoms. Those 95% of the people who were found to have a few MS scars during an autopsy, but who had no indication of disease, could simply be people who had very few BBB malfunctions. Those unfortunate people who have very rapid progress of the disease may actually be displaying a pronounced blood-brain barrier problem.

It is reasonable to assume that even when a person has what would appear to be serious blood-brain barrier deficiencies, that it most places the barrier is still effective. The deficiencies are simply isolated breakthroughs. It is sort of similar to a dike or levy starting to leak. Generally, a leaking dike only has a very, very tiny percentage of its area malfunctioning. Most of the wall is still holding. I anticipate this would hold true for the BBB as well.

With this scenario, it becomes simple to explain the erraticness of MS. The attacks occur wherever there is a breakthrough in the blood-brain barrier. It is impossible to predict where the next breakthrough will be, or how extensive the problem will be in the future. Furthermore, if a person has a borderline healthy BBB, then depending on diet and various other factors, the effectiveness of the BBB may fluctuate. Thus, with two people having similar MS symptoms, one may suddenly get better and have few attacks and the other may become steadily worse. If indeed MS is primarily indicative of a BBB problem, then the assumption would be that in the recovering person something happened to restore the effectiveness of the BBB and in the other the BBB continued to malfunction.

If a defective blood-brain barrier is a controlling cause of MS, then the current approach to MS cures are understandably ineffective. Currently, most researchers attempting to find treatments for MS are concentrating on weakening a person's immune system so as to make the attacks against his own cells less effective. Short of completely getting rid of all of a person's white cells, this will simply not be effective, as indeed it has proven not to be. Yet, with a weakened immune system, a person cannot defend himself against the various diseases we all come in contact with. And, indeed, this has been a problem. So, not only is this treatment ineffective, it is dangerous with serious side effects.

On the other hand, if the MS problem lies in large part to a defective BBB, the course of treatment should be obvious: STRENGTHEN THE BLOOD-BRAIN BARRIER.

Notice, this treatment concept is not really a cure. A person with sensitized lymphocytes is only a breach of the BBB away from another attack, and should anticipate being this way the rest of his life. However, if the BBB can be strengthened to the point that no more attacks ever occur, then for all practical purposes the disease has been controlled. Since periods of recovery are a normal part of the progress of the disease, only to be overwhelmed by new attacks, one can also assume that if no new attacks occur that a person should make continual progress towards recovery of functionality. Of course, in advanced cases where significant numbers of cells have been destroyed by scar tissue, complete recovery should not be anticipated. However, for those in earlier stages, the prospects for nearly complete recovery should be fairly high.

Furthermore, once scar tissue has formed at an attack site, the scar tissue may or may not have the same effectiveness in functioning as a blood-brain barrier as the normal brain capillaries. If it does not, this would possibly explain why there seem to be multiple attactks at the same site. It also complicates the ultimate treatment approach.

Cause of Blood-Brain Barrier Weakness
There has not been a lot of attention given in research experiments to the BBB. Therefore, what information we have tends to be spotty and should be thought of as representing only random samplings of the total picture.

One cause of BBB weakness has been reported to be a thiamin deficiency. Another has been a deficiency of certain essential fatty-acids. Apparently, during the flu or a cold the BBB may be weakened as well.

It is possible that MS could be the result of attacks by two unrelated, independent viruses. The first could occur from a bout of a disease such as measles which permanently sensitizes some of the lymphocytes against myelin. The second is an unrelated one which attacks the integrity of the capillaries at the BBB. Many researchers have tried to find an active virus related to MS attacks without success. If they were looking only at the MS attack site itself and if our scenario is true, then their problem may well have been that they were simply looking in the wrong place. In our scenario we should anticipate that the second virus would be located in the blood, perhaps lying dormant most of the time but occasionally flaring up; during a flare-up, it would then have the effect of weakening the BBB. It is known that viral activity can affect capillary integrity as a whole; in fact those who recommend taking large doses of vitamin C for warding off colds and infections claim that improved capillary strength is one of the primary benefits of vitamin C.

There may be all kinds of other factors which have not been isolated or studied which affect BBB integrity. If further research does indeed confirm the significance of BBB integrity in MS progress, perhaps this is an area in which future research should be heavily concentrated.

Strengthening the BBB--General
If our goal is to strengthen the BBB in order to prevent lymphocytes from reaching myelin, we have a fundamental problem. To my knowledge, there has been no research done concerning this specific issue as it relates to MS. The problem is that a certain nutrient might strengthen the BBB under one set of conditions pertaining to a particular experiment. However, this does not necessarily mean that it will also be effective against those conditions which caused the BBB failures associated with MS. This is particularly true if BBB breakdown is the direct result of an active viral attack. However, it does make sense to start with those things that are known to affect the BBB or capillary integrity in general and hope that these things do indeed carry over into an effective MS treatment.

If thiamin deficiencies and essential fatty-acid deficiencies and possibly vitamin C deficiencies can weaken the blood-brain barrier, then obviously the first step of treatment should be to confirm that a person has adequate amounts of these nutrients.

Strengthening the BBB- Blueberries and Grape Seeds
There is one group of chemicals which has definite experimental evidence in strengthening the blood brain barrier. This group comprises the anthocyanins, which are found in blueberries, and the proanthocyanidins, which are found in grape seeds and purple grape skins.

Bilberries, the European form of the blueberry, has been shown to be effective in strengthening capillaries throughout the entire body, including those that comprise the BBB. The anthocyanins found in bilberry are also found in blackberries, blueberries, and cherries. The anthocyanin compounds are what give the bluish color to these fruits. I do not know how much the amount of anthocyanins varies between them. However, it may be reasonable for a person desiring to strengthen his BBB simply to start consuming generous servings of these fruits, fresh or frozen, simply as a normal part of his diet. Bilberry extracts are also readily available on the market in health food stores and larger drug stores.

The proanthocyanidins are similar chemicals which are found in purple grape skins and seeds. It is also found in certain kinds of pine tree bark. The proanthcyanidins are very similar chemically to the anthocyanins and have much the same effect on the BBB. Thus, eating lots of purple grapes would be another potential treatment. Alternatively, for those who want more control over the amount of proanthocyanidin they are consuming, a standardized grape-seed extract such as those readily available on the market would make sense.

In general, it seems that one-fourth to one-half a pound of fresh, dark-blue colored fruits would make a reasonable dietary supplement. If one gets standardized herbal supplements, they typically come with recommended quantities. Other than this, it is difficult even to speculate on how much of these nutrients would be reasonable in a treatment program. First of all, the ideas here are extremely preliminary; there has been no research done to my knowledge tying these things together. Secondly, if a relationship can be established between BBB deficiency and MS, it is not known whether a person with MS is just one who has inadvertently neglected getting proper nutrients in his diet to maintain a healthy BBB or if the BBB deficiency is due to another cause. This is important, because if it is simple an inadvertent omission, then the above suggestions would seem reasonable. If it is due to another cause, then these nutritional supplements may be totally worthless or needed in special quantities. At this point in time, these are all unknowns. Finally, it is possible that once scar tissue is formed at a site, that there will be a permanent weakening of the BBB at that local. So, these nutrional suggestions may have some value for reducing the probability of new attack sites forming but be of no value where the BBB has been permanently damaged.

Strengthening the BBB -- Garlic and anti-viral Herbs
If MS attacks are the result of weakened BBB due to nutritional deficiencies, the treatments of the two preceding sections would be expected to be effective. However, if BBB breakthroughs are the result of a viral attack, it is possible that such an attack could overwhelm even an otherwise quite healthy BBB. In this case we should look to treatments which can improve a person's resistance to viral attack.

In many ways I hope that simply strengthening the BBB through proper nutrition will be found to be effective. I have less intuitive confidence in the potential effectiveness of treatments proposed in this chapter so that I am hesitant about them. Yet, in science, intuition can be dangerous because it is so often wrong, and the following discussion is provided for completeness' sake.

The approach of this section is simple. Here, we assume that some type of viral attack degrades BBB integrity and that even an otherwise healthy BBB cannot stand up to the attack. The goal of treatment is simply to strengthen a person's body against viral attacks through the use of Herbs and nutritional supplements. There is indication that Herbs can sometimes have value in reducing a person's susceptibility to viral attacks. However, diseases such as herpes and AIDS show that even when a known virus is the cause of a problem, we can not always do very much about it. Thus, I hope that the discussion of this chapter will be irrelevant and not needed because of adequate response to the earlier proposed treatments.

It should be recognized that there could be differing causes of BBB failure-induced MS attacks for different people. In other words, one person may have an MS attack due to a BBB failure caused by a nutritional deficiency and the next person have one due to a viral attack of the brain capillaries. Thus, effective treatment for one person may not necessarily be effective for someone else.

As a general statement, there are two approaches for using herbs to deal with viruses. One is short termed for dealing with a specific problem. The other is long term, where a person simply attempts to improve his underlying resistance to viral attack. There is a difference between the two approaches.

Two of the most powerful herbs against viruses, licorice and St. John's Wort, have complications such that long term usage cannot be recommended. If one were to know in advance that he had an impending viral attack which would cause an MS flare-up, these Herbs might have value. However, once the flare-up has started, it is to late for these Herbs to do any good. Hence, they are not recommended.

By contrast, there are other herbs that have good anti-viral effects and tend to promote good health in a number of other areas as well. These herbs could tentatively be used on a long-term, permanent basis for their general benefits to health. Their anti-viral activity simply offers an added, extra benefit. Specifically, these are garlic, echinacea, and panax ginseng.

A. Garlic. There has been some indication that garlic consumed at the level of around two cloves per day can be helpful in warding off viral infections. The major problem with garlic is the odor given off by those consuming it. Some garlic extracts available at health food stores and drug stores claim that they reduce or eliminate the odor. Onions have much the same effect as garlic, but apparently at only one-tenth the potency.

B. Echinacea. This is a North American herb used extensively by the Native Americans for treating many ailments and seems to have some effectiveness in reducing viral attacks.

C. Panax Ginseng. This chinese herb seems to also be helpful in strengthening a persons body against viral attack.

Again, these recommendations are nothing more than "shooting in the dark". Their value lies in the fact that they are inexpensive, readily available, tend to be good for a person's health on their own merits and may have some value for the MS patient. Treatment with these herbs is a reasonable place to start until more research results give us a basis for a different course.

Herbs to reduce inflammation.

In general, almost all of the herbs mentioned for their anti-viral capabilities also reduce inflammation in a generalized sense. In particular, both garlic and echinacea have demonstrated anti-inflammatory effects. So, the recommended treatment of garlic, echinacea and panax ginseng for anti-viral effects carries along with it a certain amount of anti-inflammatory activity as well. However, the actual effectiveness of these in reducing the damage from an MS attack is completely unknown.

Oxygen to reduce inflammation.
During an MS attack there is typically substantial inflammation at the location where the lymphocytes are destroying the myelin. There is some indication that myelin could have a tendency to reform after the attack were it not for the scar tissue left behind. There is also indication that the scar tissue is formed because of the inflammation. Hence, if one could reduce the level of inflammation during an attack, it may be possible to reduce the some of the long-range impact of the attack. Much about this is speculative and not well documented. Several studies have been made concerning the effectiveness of drugs that typically reduce inflammation, but their effectiveness has not been encouraging. That does not necessarily mean that the concept is invalid, it could merely be that the particular drugs tested happened to be ineffective at an MS site, whereas a different one might yet prove to be effective.

This is where Oxygentherapy comes into the equation. Oxygen is essential to every one of the tissues in the body and that any tissue injury requires oxygen for healing. Recent research in the University of Dundee has shown that, in the inflammation that is typical of MS, the transport of oxygen is severely limited by tissue swelling.

It has been shown that, despite the blood flow increasing many times, there may be a severe lack of oxygen in the affected area so that, just when oxygen is needed most, it cannot reach the tissue in sufficient quantity.

Oxygen therapy, where the normal amount of oxygen in the air is many times exceeded, is now being widely used in medical practice, notably in the USA, Europe, Japan, Russia and China primarily to treat carbon monoxide poisoning and aid the healing of injuries and wounds of different types. It is being used increasingly in neurological diseases such as stroke and in head and spinal core injury.

Its use in Multiple Sclerosis has been controversial, largely because its function and the expectations of its effects have been widely misunderstood.

However, studies have shown that it is beneficial. The process by which damage to the nervous system is caused in MS clearly cannot be prevented by oxygen therapy, but, as already discussed, the body normally heals itself using oxygen from the air - giving additional oxygen extends the body's ability to heal and can limit some of the damage which the disease causes.

Summary

If human suffering and life were not at stake, it would make sense to attempt to get formal research programs to establish the validity or invalidity of these ideas. Fortunately, the treatments proposed are things which a person may normally want to consider doing anyway, just for the sake of potentially greater health in general. The treatments are relative inexpensive, promote greater health in general, and are anticipated to have minimal side effects.

The information on this page is informational. It suggests treatments based on new concepts which would ideally be performed under controlled experimental conditions under the direction of qualified medical doctors and medical research scientists. It is in the hope of making these concepts known to the public that interest in such a project and the funds to do it properly may develop.

Because MS patients so typically have spontaneous periods of remission where it can appear that the disease has completely disappeared, only to have it come back later, it is difficult to truly assess the value of a particular treatment. What appeared to be effective treatment may have actually been mere coincidence, where an ineffective treatment was errantly given credit for what was actually a spontaneous remission.

There is one form of evidence, though, which would be truly significant. If a person had had an MRI shortly before the treatment started, and after a significant time had his symptoms disappear and also had an MRI that showed the disease had stopped its progress, then this would be exciting. This is something that only time may tell.

The format for this page was taken from: Multiple Sclerosis: Blood-Brain Barrier Deficiency as a Possible Cause and Potential Treatments
by Tim Stout, B.S.
Additional information about Oxygen Therapy by Colin Russell

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