How Stress Causes Brain Inflammation

Where the Brain, Immune & Hormonal Stress Response Meet

I took this photo from a train near Flam, Norway.

In this newsletter, I’ll break down the key players in brain inflammation, how these players work together, and how they can ultimately disrupt neuronal communication.  I’ll discuss:

• The beneficial role of inflammation.

• The bridge between the brain and immune system - mast cells & microglial cells.

• The bridge between the immune system and our hormonal stress response - Corticotropin Releasing Hormone (CRH).

• How head injury, toxicity, problematic microbes, and emotional and psychological stress contribute to brain inflammation.

With this groundwork laid, in an upcoming newsletter, I’ll discuss the many ways we can lower inflammation in the brain.

1. Inflammation 

Inflammation is actually a good thing. It is a protective response to injury or infection. It helps remove the problem (toxin, infection, damaged tissue) and start tissue healing.  It gets a bad rap, however, because of the collateral damage it causes when it’s trying to protect us from overwhelming toxins, problematic microbes and/or chronic stress.  If these aren’t dealt with or removed by other means, inflammation will simply persist. 

As you can see, there needs to be much more attention to why we are inflamed and not just that we are inflamed.

2. Neuro-inflammation

This is when the central nervous system (the brain and/or spinal cord) is inflamed.  Neuroimmunology is the study of this interface between the immune system and the central nervous system. The two cells at this interface are mast cells and microglial cells.

3. Mast Cells

As part of the immune system, mast cells mediate immune, allergic and inflammatory responses. Though not in the brain, they are everywhere else in the body.  They are especially concentrated in areas in direct contact with the outside world - the skin, and the respiratory, digestive and urinary tracts.  Their job is to pick up information about perceived threats from the tissues and quickly communicate that information to other tissues. Such threats can be temperature extremes, toxins, unwelcome microbes, chemicals, emotional stressors, EMF, and other insults.  How reactive they are can depend on how much “threat” our body is already dealing with. Mast cells communicate with other cells and tissues (in other parts of the body) by releasing inflammatory mediators.  

Mast cell activation occurs in asthma, allergy, arthritis, cardiovascular disease, interstitial cystitis, psoriasis, atopic dermatitis, cancers and metastasis, endometriosis, ulcers, prostatitis, periodontitis, irritable bowel syndrome, inflammatory bowel disease and many other chronic health conditions.  Mast cells play a role in traumatic brain injury, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and other forms of dementia, sleep disorders, migraines, pain, ADHD and autism.  Major depressive disorder, bipolar disorder, and schizophrenia, are all associated with increased inflammation.    Mast Cell Activation Syndrome (MCAS), occurs when someone is reacting to multiple triggers and having multiple symptoms from different body systems.   When someone has MCAS, they may feel like they are “reacting to everything,”

4. Inflammatory Mediators

These messengers, which are released from mast cells, communicate with other cells and tissues, and can result in a range of  symptoms. It would be unusual for me to see someone with brain symptoms who doesn’t have evidence of inflammation in other parts of their body as well.  You may recognize the names of some of these: histamine, tryptase, chymase, tumor necrosis factor-alpha (TNF-alpha), serotonin, heparin, proteoglycans, vascular endothelial growth factor (VEGF), IL-1beta, IL-8, IL-33, chemokine, ligand 2, CCL3, CCL5, GM-CSF, metalloproteinase (MMP’s), ROS, substance P, dopamine, TGF-beta, corticotropin-releasing hormone (CRH), neurotensin, prostaglandin D2, leukotrienes, and more.  

5. Microglial Cells 

Mast cells can also activate microglia (the immune cells in the brain).  Their job is to remove damaged neurons, waste, and things that aren’t supposed to be there, and to keep the brain healthy.  Too much activation means too much cleaning up. Excessively scrubbing any part of your body leads to inflammation and then tissue destruction - in this case brain cells/tissue. In the short term, inflammation causes disrupted connections between neurons leading to symptoms.  A major insult to the brain (head injury, emotional stress, toxicity) can result in microglial cells becoming “primed.”  Primed microglial cells will respond more rapidly and dramatically to the next insult. This looks like more abrupt and severe symptoms of brain inflammation.  If inflammation goes on too long, nearby neurons will die which leads to…

6. Neurodegeneration 

This is when nerve cells stop working or die due to chronic inflammation. Over years, this evolves into dementia. Dementia doesn’t start shortly before the onset of memory loss.  It is years in the making. Alzheimer’s Disease, Parkinson’s Disease, and ALS are the result of neurodegeneration.  

7. Neuro-immunoendocrinology & Psycho-neuroimmunoendocrinology

Neuroimmunoendocrinology is the study of the interface between the immune, central nervous and endocrine (hormonal) systems. These systems can influence each other in many directions. Here, I’m focusing on a stress hormone from the brain that activates the immune system, which as just discussed, can act on the brain and the body. 

Psychoneuroimmunoendocrinology is the study of how psychological and emotional stress can cause this stress hormone to be released from the brain and again activate the immune system. When you hear, “stress causes inflammation” - that’s what we’re talking about.  So what is that hormone?

8. Corticotropin Releasing Hormone (or Factor) CRH

This is a hormone released from part of the brain when we are under stress (physiologic or emotional). Its job is to tell the adrenal gland to make more cortisol.  If our adrenal glands are unable to keep up with demand, more CRH is released.  There are receptors for CRH on mast cells and on microglial cells. When it hits those receptors, it activates those cells to do their thing, which is to create inflammation.

This helps explain how emotional stress causes “inflammation” and why lowering inflammation in the body and brain requires lowering stress in our lives and addressing our stress response. In short, supplements, medication and dietary changes alone are not enough. This is why I try to balance the left brain scientific details with the right brain big picture of our healing.

RCCX theory suggests that about 15-20% of the general population has more CRH released when we are under stress because of a weakened 21-hydroxylase gene (that results in an inability of our adrenal glands to keep up).  This means a greater vulnerability to mast cells and microglial activation, leading to more inflammation, more brain related symptoms and certain health issues. This means we need to be more intentional about lowering our stress response, as well as avoiding toxins and keeping our microbiome healthy.  RCCX theory argues that most people with brain related conditions have this vulnerability.

9. Tipping Point

As long as things are in a relative balance, our immune system plays its protective role.  When the burden or threat exceeds the body's ability to manage or remove the burden, inflammation will persist.  Examples:

• Too much toxicity (chemical, metal, or from mold, yeast or other microbes). This is impacted by the food we eat, the water we drink, the air we breathe, the products we put on our skin, the electromagnetic fields we are exposed to, the health of our microbiome, etc. 

• Unwelcome microbes that aren’t easily removed (Lyme, certain viruses, mold, yeast overgrowth).

• If we are chronically stressed, have a traumatic event, or have a dysregulated stress response from inadequate or disrupted early attachment.

• A combination of any of these.

• Structural issues such as misalignment of the upper cervical spine can also be a factor for some. Not only is this a stress on the body, it can impact the vagus nerve, which is one of the things that help keep mast cells in check.

10. Intersections:

• Autoimmune psychosis, PANS, and PANDAS involve inflammation. In their case, however, specific antibodies are targeting specific parts of the brain. This is beyond what mast cells and microglial cells are doing.

• Walsh Nutrient Imbalances - You may be wondering if inflammation is such a big player in brain conditions, why is it that the Walsh approaches, which address nutrient imbalances (methylation imbalances, high copper, low zinc and pyrrole disorder), and neurotransmitter functioning are so helpful for so many people with brain conditions.  Aside from addressing oxidative stress, which itself is inflammatory, optimizing zinc, optimizing methylation, lowering copper, and lowering pyrroles, improves our stress tolerance and thus further lowers inflammation. 

But, there are many other ways to lower inflammation, that I look forward to sharing in an upcoming newsletter.

As always, I’d love to read your thoughts or questions.

Until next time,

Courtney

Medical Disclaimer:

This newsletter is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis or treatment for either yourself or others, including but not limited to patients that you are treating (if you are a practitioner). Consult your own physician for any medical issues that you may be having.