- Why inflammation leads to a leaky blood-brain barrier: MicroRNA-155
- What is the Blood Brain Barrier?
- Is a “leaky brain” causing your brain problems? – Holistic Wellness Center of the Carolinas
- The protective barrier you never knew you had
- What causes a leaky brain?
- How to support a healthy blood-brain barrier
- Signs You Might Have A
Why inflammation leads to a leaky blood-brain barrier: MicroRNA-155
Until now, scientists have not known exactly how inflammation weakens the Blood-Brain Barrier, allowing toxins and other molecules access to the brain.
A new research report appearing in the June 2014 issue of The FASEB Journal solves this mystery by showing that a molecule, called “microRNA-155,” is responsible for cleaving epithelial cells to create microscopic gaps that let material through.
Not only does this discovery help explain the molecular underpinnings of diseases multiple sclerosis, but it also opens an entirely new avenue for developing therapies that can help penetrate the Blood-Brain Barrier to deliver lifesaving drugs.
According to Ignacio A, Romero, Ph.D., “We are beginning to understand the mechanisms by which the barrier between the blood and the brain becomes leaky in inflammatory conditions.
these and other findings, drugs that reduce the leakiness of the barrier have the potential to improve symptoms in many neurological conditions.
” Romero is one of the researchers involved in the work from the Department of Life, Health and Chemical Sciences of the Biomedical Research Network at The Open University in the United Kingdom.
To make this discovery, Romero and colleagues first measured microRNA-155 (miR-155) levels in cultured human cells and compared them to cells under inflammatory conditions.
Researchers then measured levels in the blood vessels of inflamed brain areas of patients with multiple sclerosis (MS) and compared them to non-inflamed areas. In both cases, miR-155 was elevated in inflammation. Then, in mice, normal mice were compared with mice that were genetically altered to lose miR-155.
When an inflammatory reaction was induced in these two groups of mice, the mice that could not express miR-155 had a much reduced increase in “leakiness” of the Blood-Brain Barrier than normal mice.
Finally, scientists investigated in cultured human cells the mechanism by which miR-155 levels cause leakiness of the barrier and concluded that miR-155 affects the organization of the complex structures that form the tight connections between endothelial cells.
“This study has the potential to be a game-changer in terms of how we treat neurological conditions and how we deliver drugs to the brain,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal.
“Since it was first discovered, the Blood-Brain Barrier has always been a touch elusive.
Now, after careful analysis, we are learning exactly how our bodies keep our brains safe and that microRNA-155 is a key player.”
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Materials provided by Federation of American Societies for Experimental Biology. Note: Content may be edited for style and length.
- M. A. Lopez-Ramirez, D. Wu, G. Pryce, J. E. Simpson, A. Reijerkerk, J. King-Robson, O. Kay, H. E. de Vries, M. C. Hirst, B. Sharrack, D. Baker, D. K. Male, G. J. Michael, I. A. Romero. MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation. The FASEB Journal, 2014; DOI: 10.1096/fj.13-248880
What is the Blood Brain Barrier?
Many of us know about ‘leaky gut’, but did you know that the same mechanisms that can increase your gut lining permeability exist with your brain lining? We all have a membraneous filter that separates our circulating blood from the precious extracellular fluid that circulates around the brain. This finely woven mesh of astroglia cells and blood vessels surrounds and protects the brain, allowing only allow nano-sized particles in or out as needed and keeping harmful larger substances such as bacteria and neurotoxins out.
Just the gut lining, this blood brain barrier is composed of ‘tight junctions’ between cells that can open to selectively permit molecules necessary for neural function into the brain.
The blood brain barrier is extremely vulnerable to many aspects of modern life, such as systemic inflammation and high cortisol from chronic stress. These and other factors can degrade the integrity of the tight junctions, creating an effect very similar to leaky gut.
When this happens, toxins, microbes and other substances that normally would bounce off a healthy blood brain barrier are able to pass through, activating an inflammatory response inside the brain.
Evidence is also emerging that indicates the amyloid plaques in the brain characteristic of Alzheimer’s disease may be forming at least in part to stave off infection from bacteria, viruses and yeast.
Immune reactions to gluten can also lead to a ‘leaky brain’. Zonulin is a protein that opens up the tight junctions in the blood brain barrier (and in the intestinal lining), thus regulating how permeable the barrier is.
For people with celiac disease and gluten sensitivity, gluten triggers zonulin to open these junctions.
Importantly, many researchers believe zonulin release isn’t specific to the gluten intolerant population – some research suggests that gluten opens these junctions in all people.
In addition to stress, gluten and systemic inflammation, other factors that degrade the blood brain barrier are elevated homocysteine (homocysteine, measured by a simple blood test, is an inflammatory compound that elevates with B vitamin deficiency), alcohol, poor diet and antioxidant status, advanced glycosylated end products (these are free radicals created with elevated blood glucose where the glucose cannot enter the cells), and harmful free radical compounds such as pollutants, all of which trigger inflammation. The most common symptoms of a leaky blood brain barrier are brain fog or reduced brain function after exposure to environmental insults such as inflammatory foods, gasoline fumes or chemical cleaning products.
Testing for a Leaky Blood Brain Barrier
The tight junctions of a healthy blood brain barrier only allow nanoparticles, which are very tiny, to pass through while preventing the passage of antigens and harmful environmental compounds.
GABA, a supplement popular for producing a calming, relaxing effect, exceeds the nanoparticle size and does not have a blood brain barrier transport protein. Therefore, it should not be able to cross a healthy blood brain barrier.
If you take GABA and notice it has an effect, you probably have a leaky blood brain barrier.
To test this, take 800-1,000 milligrams of GABA and give yourself a two to three hour window to see whether it affects you.
Feeling no change after taking GABA is a good sign your blood brain barrier is intact, while feeling either more relaxed and sedated or anxious and irritable indicates a permeable blood brain barrier. It can be useful to do the GABA challenge periodically to see how various things might affect you.
For instance, if you’re gluten intolerant a GABA challenge can show you that eating gluten will cause leaky brain for a week or two. However, try not to take GABA regularly or you risk shutting your GABA receptor sites.
Healing Your Blood Brain Barrier
The good news is that even though the blood brain barrier degrades quickly, it has to potential to regenerate quickly. For instance, high stress degrades the blood brain barrier, but normalizing stress can allow it to repair.
It’s important to note that ‘stress’ in this sense is not just mental-emotional stress, but also physiological stress which can be induced by infections, lack of sleep, food sensitivities, gut bacterial imbalance and leaky gut, constantly fluctuating blood sugar, and smoking and other lifestyle factors – it’s all the same to your body, which creates an immune response in an attempt to get back to homeostasis. Simply stabilizing your blood glucose and cortisol levels, reducing inflammatory triggers such as gluten, clearing up a gut infection or chronic virus, boosting dietary antioxidants and supplementing with flavonoids proven to dampen inflammation can help restore the blood brain barrier and protect your brain.
Is a “leaky brain” causing your brain problems? – Holistic Wellness Center of the Carolinas
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You may have heard how important it is to heal a leaky gut, but it’s just as important to address permeable blood-brain barrier, or a “leaky brain.” Linked to a variety of chronic health issues, leaky brain is a surprisingly common problem that can be addressed with proper anti-inflammatory dietary and lifestyle modifications.
The protective barrier you never knew you had
The blood-brain barrier is a protective layer in the circulatory system of your brain, serving to filter and block harmful substances while allowing beneficial nutrients to pass into the brain and cellular debris to pass out.
However, certain circumstances can break down the blood-brain barrier and cause it to become hyper-permeable, or “leaky.”
When unwanted substances enter the brain, they can cause brain inflammation linked to conditions such as:
- Brain fog
- Headaches and migraines
- Cognitive impairment
- Parkinson’s disease
Schizophrenia and other psychological disorders
What causes a leaky brain?
More and more functional medicine patients are becoming familiar with leaky gut. If you have leaky gut, chances are you have leaky brain too as similar mechanisms cause it.
Leaky gut and leaky brain frequently occur together as their root causes are similar:
- Chronic stress
- Systemic inflammation
- Poor diet and antioxidant status
- Head trauma
- Elevated glucose and diabetes
- Elevated homocysteine from B vitamin deficiency
- Environmental toxins
- Heavy metals
- Autoimmune disease
- Oxidative stress
- Food additives
- Sleep issues
- Chronic infections
- Excess alcohol consumption
If you have any of the symptoms of leaky brain and this list of causes rings some bells, then it’s worth looking into how to support the health of your blood-brain barrier.
How to support a healthy blood-brain barrier
While the number of leaky brain causes and symptoms may seem daunting, the good news is the brain is very receptive to simple healing protocols. There are a number of things you can do to help heal a leaky blood-brain barrier:
Heal your leaky gut. Leaky brain and leaky gut happen for the same reasons. A focused healing protocol for leaky gut often resolves symptoms of leaky brain.
The gut and brain are intimately connected via the “gut-brain axis,” a two-way communication pathway along the vagus nerve, which leads from the base of the brain to all the major organs.
When either the brain or gut is order, it can affect the function of the other. Therefore, it’s important to support your digestive health.
You can help support your gut health through the following:
- Eat plentiful and varied vegetables (and just a bit of fruit) to give healthy bacteria in your gut the fiber they need.
- Supplement with a high-quality probiotic.
- Consume fermented foods such as kimchee, kombucha, and water kefir to support a healthy gut environment.
Avoid gluten. Gluten is highly inflammatory and one of the worst foods for the brain (and the gut):
- It elevates zonulin, the protein your body produces to increase barrier permeability.
- Many studies confirm that gluten leads to the neuroinflammation behind many psychiatric problems.
- Gluten sensitivity can also result in negative changes to white matter in the brain associated with neurologic disorders such as multiple sclerosis.
If you aren’t convinced, try following a gluten-free diet for 30 days and see how you feel. Caution: Gluten is hidden in many foods, so make sure you understand everything on food labels.
Avoid reactive foods. The inflammation from food sensitivities can cause leaky blood-brain barrier. To find out if you react to certain foods, ask our office about food sensitivity testing or an elimination-reintroduction diet.
Sleep. Deep sleep is one of the most important factors for brain health. Sleep deprivation is linked with impaired blood-brain barrier function and permeability.
To maximize your sleep, incorporate the following daily habits:
- Get at least 7-8 hours of sleep per night.
- Avoid blue screens in the hour before bed.
- Use blue-blocker glasses later in the evening.
- If you must use a screen at night, install the F.lux app.
- If you suffer from blood sugar instability, have a small high-protein snack just before bed.
Manage stress. Chronic stress is one of the greatest enemies to your brain health. Stress degrades the blood-brain barrier and can cause brain inflammation.
To help manage your stress load:
- Take an honest look at your stress factors, such as a toxic friendship, a negative job, worrying too much, a bad marriage, or over-commitment as a volunteer. Decide what you can eliminate or reduce and take immediate steps.
- Support the adrenal glands with adaptogens such as panax ginseng, Siberian ginseng, ashwagandha, holy basil leaf extract, rhodiola, and boerhaavia (punarnava).
- Adopt a daily stress-reduction practice such as yoga, meditation, qi gong, deep breathing, laughter, and play.
Avoid alcohol. Alcohol can weaken and degrade the blood-brain barrier.
Caffeine. Studies show that caffeine can be protective against dementia, Alzheimer’s and Parkinson’s disease by keeping the blood-brain barrier intact.
Because caffeine can disrupt sleep function it’s important to moderate caffeine consumption and make sure to consume it early in the day.
Note: Some people can’t tolerate coffee because it can contain toxic byproducts made by mold called mycotoxins, so take note of how you feel after drinking it.
Avoid environmental mold. Environmental mold and the mycotoxins it produces can reduce the integrity of the blood-brain barrier and cause neurologic damage.
Toxic mold is not always easy to identify, so If you live, work, or study in a building where you suspect mold toxicity, consult with a mold expert to determine if your space is safe.
To help mitigate the effects of mold exposure:
- Move the house or find a new job location
- Use a HEPA-grade air purifier
- Support your liver detox pathways
Ask my office about more functional neurology strategies to support your blood-brain barrier health.
Signs You Might Have A
It's easy to take for granted what a brilliant biological machine the brain is. This amazing organ manages every aspect of your body — from your thoughts to your hormones, muscles and digestion.
Sadly, diseases of the brain are rampant in our society.
The National Institute of Mental Health estimates that close to 20% of American adults currently suffer from a diagnosable mental disorder. And the U.
S shells out around $113 billion every year on mental health treatment.
These figures don't even factor in the cost of autoimmune brain problems Alzheimer's, Parkinson's, Multiple Sclerosis and autism — which are affecting more people every year.
With an increasing number of brain health problems we have to ask: why? Functional medicine is concerned with investigating the root causes.
Leaky Brain: A New Understanding of Mental Health
I have written in the past about leaky gut syndrome. Now research is finding that a leaky gut can also be associated with a “leaky brain,” or the destruction of the protective blood-brain barrier (BBB).
The Gut-Brain Connection is a foundational system to address for brain problems. Occludin and zonulin are two proteins that help determine both gut lining and blood-brain barrier permeability. Elevated antibodies against occludin and zonulin are one way to gauge leaky brain syndrome.
Researchers are also looking at a molecule called microRNA-155, which is elevated with inflammation. This molecule can create microscopic gaps in the blood-brain barrier that let material through. This permeability can cause your brain's immune system to work in overdrive, leading to brain inflammation.
The area of medical research known as “the cytokine model of cognitive function” looks at how brain inflammation is associated with cases of depression, anxiety, brain fog and autoimmune brain problems.
For example, researchers are looking at how inflammation decreases the firing rate of neurons in the frontal lobe of the brain in people with depression. In cases of neurogenic inflammation, medications antidepressants are often ineffective because they aren't addressing the underlying brain inflammation.
In other words, if you suffer from depression, anxiety, brain fog or an autoimmune brain problem, blood-brain barrier permeability (leaky brain syndrome) should be considered.
I Think I Have Brain Inflammation. Now What?
Here are some action steps you should consider taking for brain health:
1. Conduct labs to assess your blood-brain barrier.
Blood-Brain Barrier Proteins: I run these labs to help determine if the blood-brain barrier has been breached.
Occludin and Zonulin: Blood tests can measure antibodies against these two proteins, which determine brain and gut permeability.
Homocysteine: High levels of this amino acid have been linked with blood-brain barrier damage. Learn more about why you should get your homocysteine levels tested.
Brain Agers: Chronic inflammation accelerates your brain's aging. High blood sugar is one risk factor for blood-brain barrier destruction. I recommend having fasting blood sugar, Hgb A1C and other brain aging labs ran to know your risk factors.
2. Conduct microbiome labs.
An unhealthy gut can lead to an unhealthy brain. So looking at the other end of the gut-brain axis can uncover underlying factors that might be hidden in the “second brain”.
That's because bacterial imbalances and yeast overgrowth can have neurological implications.
For example, anxiety and depression have been linked to lower levels of bacteria called Lactobacillus helveticus and Bifidobacterium longum.
3. Avoid brain zappers.
Be sure to steer clear of common brain-damaging foods refined and sugary foods, as well as other toxins.
4. Manage stress.
Research suggests that acute stress increases blood-brain barrier destruction. Tai chi, yoga and mindfulness meditation can all be effective ways to mitigate stressful times.
5. Try targeted natural medicines.
Natural compounds such as apigenin, baicalein, catechins, curcumin, luteolin, resveratrol and rutin have all been suggested to dampen brain inflammation levels. The correct dosage will be case specific. Even with natural medicines, what works for someone else may not be right for you.
Aerobic exercise has been shown to increase a brain-derived neurotrophic factor, BDNF, which promotes the health of brain and nerve cells.
7. Cut back on alcohol.
Alcohol is stressful for the brain, and some studies suggest it can damage the blood-brain barrier.
8. Consider functional medicine.
There are no quick fixes when it comes to healing from chronic brain problems. Functional medicine customizes diagnostics and natural protocols your unique needs. Consider having a free webcam or phone evaluation to see if functional medicine might be right for you.