Inflammation is the body’s response to negative environmental stimuli. Its purpose is to eliminate the aggressor agent and to restore tissue physiology. However, when inflammation without resolution is present (i.e., chronic inflammation), we know that it has deleterious effects on surrounding tissues. Chronic inflammation in the central nervous system (CNS), known as neuroinflammation, can be particularly damaging.
What is neuroinflammation?
Neuroinflammation is defined as an inflammatory response within the brain or spinal cord that can be initiated by a variety of harmful stimuli, such as infection, disease, trauma, toxins, or stress. This complex biological response involves the activation of resident immune cells and the production of cytokines, chemokines, reactive oxygen and nitrogen species, and secondary messengers. (17)
How does neuroinflammation damage the brain?
Neuroinflammatory processes are believed to play a critical role in pathways leading to neuronal death in neurodegenerative diseases. (12)(43) In the brain, microglia—a type of glial cell—are key players of the immune response, which is intimately linked to inflammation. As the resident immune cells, microglia, monitor the microenvironment for insults (e.g., toxins, pathogens, injury, damaged or unnecessary neurons, etc.), and they are critical to overall brain maintenance. For instance, they remove dead neurons, plaques, and other cellular debris that may get in the way of neuronal signal transmission. (20)(47) However, microglia exert dual roles: they act as both guardians of brain homeostasis and as instigators of damage. (3)
How do microglia instigate damage? Through overactivation. Microglia are said to be in a steady state or in an active state. When microglia become activated or “primed,” they become inflammatory. (20)(47)
Persistent microglial activation and the production of neurotoxic mediators, such as cytokines (e.g., IL-1β, IL-6, and TNF-α), not only propels further microglial activation and proliferation but also propagates nitrosative and oxidative stress that may negatively impact neuronal mitochondria and blood-brain barrier (BBB) permeability. (12)(15)(24)(31) Not only can this neuroinflammatory process slow nerve transmission speed and reduce nerve conductivity, but also a vicious cycle develops within the brain that can ultimately result in neuronal death. (42)
Persistent microglial activation
Aside from a traumatic injury to the brain, direct triggers of microglial cells may include toxic metabolites, microbes, lipopolysaccharide (LPS), any neurotoxic substance (pollutants, heavy metals, drugs, etc.), aging, vascular occlusion, ischemia, cell death, and inflammatory cytokines. (1)(23)(29)
Blood-brain barrier compromise
Loss of BBB integrity serves as a major promoter of microglial activation. Loss of BBB integrity may occur with alcohol exposure, stress responses, elevated homocysteine, hyperglycemia, prostaglandin imbalances, and oxidative stress. These factors may lead to the infiltration by environmental compounds, dietary proteins, or pathogenic organisms, which expose themselves to microglia and activate a neuroinflammatory response. (5)(11)(21)(22)(28)(46)
Peripheral or systemic inflammation also contributes to brain inflammation and cognitive dysfunction through the production of cytokine messages. (26)(40)(42) Decreasing exposure to inflammatory stimuli may be an important first step for functional medicine practitioners. Such stimuli may include the Western diet, gluten consumption, obesity, dysbiosis, environmental toxins, psychosocial stress, excessive alcohol consumption, and poor sleep quality. (9)(10)(12)(13)(14)(20)(27)(35)(44)(48)
Natural neuroinflammation interventions
Due to the side effects associated with pharmaceutical treatments for inflammation and its awareness in a more educated public, more and more patients are seeking out natural solutions. Historical practices and modern science point to a number of natural interventions to dampen inflammatory processes and improve the brain microenvironment, including vagus nerve exercises, dietary and lifestyle modifications, and dietary supplementation.
Vagus nerve exercises
As the prime component of the parasympathetic nervous system, the vagus nerve is the longest of the cranial nerves. It extends from the brainstem and through the abdomen by way of multiple organs. It is the sensory network that tells the brain what’s going on in the organs, and it regulates the homeostasis of the “resting” state—opposite the “fight or flight” state.
There is an “inflammatory reflex” transmitted in the vagus nerve that inhibits the production of TNF-alpha and other cytokines via cholinergic anti-inflammatory pathways. (30) Electrical stimulation of the vagus nerve has been shown to reduce inflammatory cytokine production (e.g., TNF-alpha) and attenuate disease severity in experimental models and in patients with rheumatoid arthritis. (8)(30)(34)
Engaging the vagus nerve, and thereby improving “vagal tone,” is a method that functional medicine practitioners can suggest to their patients to help reduce chronic inflammation. Non-device methods that some practitioners suggest to increase vagal tone include slow diaphragmatic breathing (as done in yoga and meditation), gargling with water, or singing loudly. (7)(45)
Lifestyle and dietary improvements for neuroinflammation
Being fit and active; getting quality sleep; making healthy, organic food choices; avoiding cross-reactive dietary proteins, like gluten; and reducing stress and exposure to toxins all help reduce the potential for triggering inflammatory processes in the brain. (13)(16)(18)(26)(32)(37)(40) Additionally, there are various nutraceuticals that help reduce inflammation.
Neuroinflammation: supplementation considerations
Animal research suggests that some nutraceutical ingredients are able to cross the BBB and exert their effects directly in brain tissue or positively influence BBB integrity. These include the following:
Other nutritional compounds, such as alpha-lipoic acid (2) and ginger, (33) help reduce systemic inflammation and the circulation of inflammatory cytokines that may contribute to neuroinflammatory processes. When supplementing to address neuroinflammation, considering the totality of mechanisms at work is critical.
Neuroinflammation is a key concept discussed in Mastering Brain Chemistry, a three-day seminar developed and written by Datis Kharrazian, PhD, DHSc, DC, MS, MMSc, FACN. This seminar is designed to review the key concepts of brain chemistry and to help clinicians recognize patterns of imbalances and improve overall clinical competency in the neurochemical assessment. Consider attending this seminar for a deep understanding of neuroinflammatory processes and how to address them as well as many other areas of brain chemistry that affect mental and neurological health.
The bottom line
Emerging research continues to validate the roles of glial cell activation and neuroinflammation as major contributors to the pathophysiology of neurodegeneration. Recognizing the earliest signs of neuroinflammation, such as brain fog, depression, low brain endurance (mental fatigue), or food intolerances, and acting sooner rather than later may be the key to dampening and, in some cases, reversing the damage.
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