Neuroinfammation

What do these all have in common?

  • Brain fog
  • Difficulty reasoning/thinking
  • Overwhelming fatigue
  • Depression or anxiety
  • Issues with certain foods or exposure to everyday chemicals
  • Loss of motivation
  • Pain
  • Loss of stamina/ resilience
  • Migraines?

Quite possibly, an inflamed brain.

How does our brain get inflamed?

Let’s start out by defining brain cells. There are 4 types :

  • Neurons allow the brain to communicate
  • Microglial cells act as mediators of the immune system. In addition to their immune duties, microglial cells help clear debris and dead neurons, perform synaptic pruning, produce neural growth factor, and cleanup neurotransmitters.
  • Oligodendrocytes make up the myelin sheaths involved in transmission and protection
  • Astrocyctes regulate communications, release growth factors, respond to injury, and protect our blood brain barrier.

Turns out our brain is the most nutrient and energy-dependent organ in the body BUT also the most vulnerable to toxins and stress. If something causes microglial cells to activate, inflammation results. And it goes unchecked since there is nothing to dampen it.

A leaky blood brain barrier, mitochondrial or gut dysfunction, cholesterol issues, etc. can create susceptibility for not only neuroinflammation, excitotoxicity, mitochondrial dysfunction/oxidative stress, and ultimately–neurodegeneration. 

What is neuroinflammation?

Neuroinflammation is inflammation that affects brain function. According to Dr Datis Kharrazian, PhD, there are three levels neuroinflammation: subtle, moderate, or extreme.

  1. Symptoms of subtle inflammation may include brain fog, mental speed variations, reduced brain endurance, or brain dysfunction upon chemical exposure or certain foods.
  2. With moderate inflammation, there may be mood disorders, inability to concentrate for long periods of time, increased need for sleep, lethargy/fatigue, lack of motivation, loss of appetite, etc.
  3. With extreme inflammation, things get serious. Symptoms might include delirium, dementia, coma, seizures, or tremors/twitching.

What causes microglia cells to get triggered?

Microglial cells can activate and release inflammatory compounds in response to:

Why is microglial cell activation so harmful?

When glial cells are activated too frequently, they can get “stuck” in an activated state, leading to chronic inflammation, oxidative stress, and loss of function. Even when they calm down, they could have become “primed”, making them more susceptible to being reactivated by an even lessor event.

Primed glial cells leave the brain highly susceptible to the risk factors mentioned above. The sad part, primed glial cells symptoms often goes undiagnosed after the initial triggering event.

When primed microglial cell become activated, exposures to triggers lead to symptoms in the moderate category. This is important to understand symptoms since Lifestyle interventions and direct support are absolutely crucial in these individuals to protect the brain from potential reoccurring inflammation.

What about our blood brain barrier, isn’t it supposed to protect me?

Our brain barrier is designed to let things into the brain that we need, like glucose and ketones, and keep things out that we don’t, like toxins, pathogens, errant immune cells, foreign particles. Over time, exposures to toxins or poor diet or chronic stress or etc., may compromise its integrity. This allows unintended substances to leak through, triggering an immune reaction and neuroinflammation.

How does stress affect my brain?

Our total stress load can really take a toll. Stressors can lead to inflammation throughout the body including our brain. If you think about it, it makes sense. Basically, there are only so many resources to go around. You need them to keep you safe and alive. So if the body gets overwhelmed, one thing that happens is that the adrenals tell the thyroid to go into hibernation mode in order to sustain energy (by downregulating the production and activation of thyroid hormones). Low thyroid hormones can affect brain through all sorts of mechanisms: mitochondria function, neurotransmitters, glucose metabolism, etc.

Additionally, there is the Polyvagal Theory which causes us to metabolically freeze. Think, malaise, depression, loss of concentration, etc.

How does mitochondria and oxidative stress affect my brain?

Most people think of mitochondria as only energy factories, but they also act as a metabolic braking system, similar to our thyroid. And with reduced energy production, cells just don’t perform as well.

Cell Danger Response

With too much stress, mitochondria shift from an energy producer to crisis management. If you are healthily, no worries, only the least-damaged mitochondria tend to replicate so there is usually no obvious sign of dysfunction. But over time, the mitochondria become smaller, weaker, and more dysfunctional. They generate less energy and create more free radicals, causing us to “rust” or age.

According to Dr. Naviaux MD, over time long periods of stress may create a “cell danger response”, which further suppresses mitochondrial function (to conserve additional resources) while at the same time generating more oxidative stress due to less efficient mitochondria.

Mitochondrial Uncoupling Proteins

Since neurons are easily damaged by oxidative stress, they handle mitochondrial suppression directly through antioxidant proteins, one of which are mitochondrial uncoupling proteins (UCPs). Their job is to slow the production of energy and instead uses the resources to make heat, ultimately limiting the number of free radicals being produced. Since neurons require a considerable energy for their activities, this shutdown can lead to sensitivity, fatigue, brain fog, memory issues, mood disorder, and other symptoms.

Neurons Firing Too Close to Threshold

There is also a condition called “Neurons Firing Too Close to Threshold” that makes our brain extremely reactive to sensory stimuli. So how does that work? In addition to making heat, UCPs are also involved in calcium regulation. If calcium is not effectively cleared, it allows neurons to overreact to stimuli. How? Neurons communicate via neurotransmitters. To pass messages from neuron to neuron, the message must reach a minimum threshold before it can be sent along. To keep from sending false messages, each neuron has a “resting potential”. This means in order for a message to be sent, the stimulus must be greater than the neuron’s resting potential.

So, if the neuron’s resting potential is far away from the threshold amount needed, it would require a lot of stimulation. Conversely, if a neuron’s resting membrane potential is too close to threshold, it can fire way too easily. Either case can lead to problems. Too far away and the message is never sent, too close and it may be inadvertently triggered. Weak neurons have a resting potential too close to threshold. When this happens, folks can become more sensitive to lights, sounds, smell, taste, and touch– so they end up trying try to avoid these situations, further degrading the neuron’s health and overall brain function.

How does gut function affect my brain?

The gut and the brain are very tightly linked. Take head injury for example. According to Dr. Silverman , DC, “When a blow to the head or severe jolt causes a concussion, the damage to the neurons has a parallel in damage to the gut lining. The tight junctions of the lining almost immediately open up and become permeable. This produces inflammatory cytokines that can penetrate the blood-brain barrier, leading to additional brain inflammation. In other words, when the gut is on fire, so is the brain.”

Leaky gut

He also warns, “If the sudden intestinal permeability caused by a concussion goes untreated, the concussion symptoms will be worse, due to the additional inflammation. The gut permeability may not resolve by itself, which could contribute to making the concussion symptoms linger on for weeks instead of days. Intestinal permeability may also play a role in those patients who go on to develop post-concussion syndrome by causing ongoing brain inflammation.”

With leaky gut, we often find leaky brain. With increased dysbiosis or overgrowth of “bad” bacteria or another type of pathogen, we get greater amounts of toxins like LPS and inflammatory markers floating in our bloodstream, leaving neuroinflammation and oxidative stress in its wake.

Endotoxemia can also stimulate the production of antibodies which can cross-react with cells/tissues/organs/DNA which not only cause neuroinflammation, but potential brain autoimmunity as well.

Vagus nerve

The vagus nerve is the main component of the parasympathetic nervous system which oversees crucial functions such as mood, immune, digestion, and heart rate. It innervates a two-way connection between the brain and the gastrointestinal tract. According to Dr. Alex Vasquez DC, ND, DO, “90% of the vagal fibres between the gut and brain are afferent, suggesting that the brain is more of a receiver than a transmitter with respect to brain-gut communication.” This means our microbiome becomes a major player in brain health.

Our microbiome creates compounds, both good and bad, that travel the vagus directly to the brain. If there is some form of dysbiosis, gut inflammation or infection creating toxic metabolites, it can damage the nerve itself as well as sensitive brain as it passes through a leaky blood brain barrier (BBB).

Microbiome

The Human Microbiome Project, launched in 2008, is creating a paradigm shift in world of neuroscience. Research indicates that gut issues such as infections and inflammation, may alter the species and population density of our resident microbiota. This means that our unique biome could influence our brain activity.

Studies have shown that sensory neurons are less active in germ-free mice, and, when the mice are given probiotics to restore their microbiome, the activity levels of the neurons return to normal. A metadata study published in the 2016 Journal of Neurogastroenterology and Motility, concluded that “probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder, obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory.”

Another example of a bacterial connection is the link between antibiotic exposure and altered brain function. Per the 1997 article “Antibiotics: Neuropsychiatric Effects and Psychotropic Interactions”, documented side effects from these drugs ranged from anxiety to major depression, psychosis and delirium. It may even be that Pediatric Autoimmune Neuropsychiatric Disorders or PANDAS, which links streptococcus bacteria to OCD could be attributed to antibiotic use rather than to the bacteria itself.

How do I support microglial cell activation and neuroinflammation?

When it comes to brain, it is all about lifestyle. A brain healthy lifestyle includes reduction of alcohol intake, gentle exercise, stress reduction, and good quality sleep. In addition, support should be given to improving BBB permeability, eradicating infections, supporting hormones, reducing toxic burden, supporting immune function, increasing mitochondrial capacity, and controlling oxidative stress.

Microglial cells and Blood Brain Barrier

If neuroinflammation and glial cell priming occurs, directed supplementation that help support glial cells, BBB, gut function, and neuronal function is crucial.

Exercises that directly help any affected parts of the brain may be highly beneficial in restoring lost function.

Healing of the blood brain barrier is fundamental and may be accomplished with sleep, vagus nerve activation, mitochondria rebuilding, and directed supplementation.

Neurons Firing  too Close to Threshold

Exercises that provide slow, well controlled exposure to triggers—-lights, sounds, smell, taste, and touch have been useful in calming down overactive neurons.

Vagus Nerve and Vagal toning

Vagal tone is important for overall brain dysfunction.

According to 2018 edition of Frontiers in Psychiatry,” There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency.

Since the vagal tone is correlated with capacity to regulate stress responses it can be influenced by breathing, meditation and yoga to improve resilience and the mitigation of mood and anxiety symptoms.

Mitochondria and Hormetic Stress

Finally, we should not dismiss the importance of restoring mitochondria function.

Not much of a surprise sleep, diet, exercise, stress reduction techniques, detoxification/gut support, antioxidant support and something called hormetic stress are our go to.

Hormetic stress

Hormetic stress involves creating a transient burst of reactive oxygen species that stimulate our cellular antioxidant defense system. This in turn stimulates the cells to repair the damaged and dysfunctional parts– leading to the production of greater numbers of stronger, healthier mitochondria.

Keep in mind, aging can also cause us to lose vital mitochondria. Between the age of 40-70, people typically lose 1/2 of our mitochondrial capacity, so there is another great reason to integrate activities such as exercise, intermittent hypoxic training, sauna, intermittent fasting, cold therapy or UV light in your overall protocol.

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