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Mast Cells, Stress, and Chronic Neuro-inflammation

Mast cells are a type of immune cell in the body. They are exceptionally pervasive and rightfully so as they are integral for a healthy and robust immune response. Unfortunately in mast cell activation syndromes, histamine intolerance, or other conditions with mast cell hyper-reactivity numerous adverse effects are common.

While I’ve discussed before the common symptoms associated with mast cell issues, here I’d like to discuss the relationship between mast cells and neuroinflammation.

As I remind the clients I work with on a daily basis, our body is interconnected. Every system “talks” to each other. We are a superorganism and every different system needs to be considered and accounted for when assessing overall health and proper functioning.

Mast cells have multiple different triggers, one of which is stress. Stress can come in many forms- work, relationships, food allergens, chronic infections, emotional trauma, physical trauma, finances, public speaking, a global pandemic. There are so many different types of stress, but at the end of the day-- stress is stress.

“Stress activates hypothalamic-pituitary adrenal (HPA) axis and releases corticotropin-releasing hormone (CRH) from hypothalamus and in peripheral system, which increases the formation of Aβ, tau hyperphosphorylation, and blood-brain barrier (BBB) disruption in the brain. Mast cells are implicated in nociception and pain. Mast cells are the source and target of CRH and other neuropeptides that mediate neuroinflammation. Microglia express receptor for CRH that mediate neurodegeneration in AD.”1

Put more simply, stress activates different pathways in the brain that lead to a more permeable, or “leaky”, blood brain barrier. This then allows for greater influx of mast cells and potentially pathogenic agents which trigger inflammation. “Once in the hypothalamus those activated mast cells produce more CRH, further tweaking the hypothalamus and producing compounds such as histamine, tryptase and mtDNA which send the microglia into a frenzy, causing them to release inflammatory cytokines/chemokines (IL-1B, IL-6, CCL2) that further disrupt hypothalamic functioning.”2

Thus, not only does the stress trigger the neuroinflammation but the neuroinflammation perpetuates itself until essentially the brain is on fire with excitatory and inflammatory chemicals. Neuroinflammation in turn is associated with fatigue, brain fog, and even anxiety & depression3.

Now, how do you stop it? You address the stress triggers.

This is the biggest thing I do with the clients I work with. I help them “peel back the onion layers” to determine sources of chronic infection, food allergens, improve mental health/relationships, etc. Our goals is to reduce imbalances triggering stress, as well as, improve resilience to stress (since it will always be there). In addition to this, I help them appropriately dose mast cell stabilizers either in the form of supplements (eg curcumin, luteolin, quercetin) or pharmaceuticals (eg cromolyn sodium, monteleukast/singulair) when indicated for their specific case.

Other adjunctive treatments like IV glutathione & nutrient IVs, hyperbaric oxygen therapy, and even low-dose naltrexone can also be exceptionally supportive in squelching neuroinflammation while working on the root cause.


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