The Science of Neuroinflammation

What is Neuroinflammation?

Neuroinflammation is an inflammatory response that involves brain cells such as neurons and microglia. Inflammation is an essential part of our biological process in response to infections, trauma, or injury.  One of the inflammation tasks consists of eliminating the invading pathogens and afterward promoting angiogenesis and wound healing. Interestingly, in the first stage of neuroinflammation, neurons carry out cellular debris and balance the production of cytokines and proteases.

But what is exactly what happens in neuroinflammation? What are the factors that contribute to the appearance of this environment? What can I do to mitigate the effects?

Microglia: These neuronal cells are macrophages; they patrol in our brain and help with neurogenesis regulation, synapses remodeling, and phagocytosis. They play an essential part in defense and repair mechanisms; they are known to carry out our brains’ debris.  Microglial cells have two stages: the inactivated stage or resting microglia and activated stage.

Microglia can become activated by:

• presence of pathogens.
• Tissue damage.
• Abnormal stimulation.
• Infection.
• Injury.
• Leaky gut.
• Chronic inflammation (obesity, atherosclerosis).
• Traumatic brain injury. TBI

For example, gram-negative bacteria translocate through the barrier it carries lipopolysaccharides (LPS) on its membrane. These LPS induce an inflammatory response when it comes in contact with the toll-like receptors (TLR). When the TLR4 on the microglia surface binds to LPS, it leads to the activation of NF-κB. Therefore, NF-κB initiates the production of pro-inflammatory cytokines, chemokines, and inducible enzymes that produce nitric oxide and COX-2.

Activated microglia change from a ramified inactivated state to a phagocytic state, in which they lose their ramification properties and enlarge. Accordingly, in this state, activated microglia release large quantities of pro-inflammatory cytokines that contribute to a long-term neuro-toxic state and, lastly, cause neurodegeneration. Subsequently, when glial cells become activated by an inflammatory mechanism and lose their ramified phenotype, and there is no way they can go back to their resting state. Therefore, once they become activated, any secondary inflammatory mechanism can cause severe effects.

The science of neuroinflammation is complex. Understanding the deep complex science is imperative if providers treat patients with neurodegenerative disorders. Watch this video and understand the genesis of neuropathologies.

Activated microglia have been classified into two: M1 and M2.

Classification
M1: pro-inflammatory phenotype	M2: anti-inflammatory phenotype
§  Classically activated. §  stimulated by interferon-g and TNF-a. §  initiates a first-line immune response. §  Pathogen elimination. §  Neuroinflammation.	§  Alternatively activated. §  Stimulated by IL-4. §  Involved in regulated macrophage response and wound healing. §  Restoring homeostasis.

Astrocytes, another member of the glial cell family, releases TNF-a, which promotes an inflammation response.

Blood-brain barrier and peripheral inflammation:

 

The blood-brain barrier (BBB) was initially thought to be separated from the central nervous system. Nowadays, it is known that the BBB is permeable to pro-inflammatory cytokines produced by peripheral inflammation. Ultimately these peripheral inflammation cytokines that cross the BBB can initiate synaptic impairment, neuronal death, and damaging effects that traduce on chronic diseases such as Alzheimer’s and multiple sclerosis.

Nevertheless, when a large amount of pro-inflammatory cytokines like TNF-a, IL-6, IL-1 are present, the integrity of BBB can be compromised and become more permeable. These findings have shown that cytokines affect the resistance of tight junctions in endothelial brain cells.

Neuroinflammation symptom scale:

 

Subtle	Moderate	Severe
§  Brain fog. §  Variation of mental speed. §  Reduced brain endurance. §  Brain fatigue. When exposed to specific food proteins, chemicals, scents, or pollutants.	§  Depression. §  Inability to concentrate. §  Increased demand for sleep. §  Lethargy and fatigue. §  Lack of motivation and appetite.	§  Delirium/confusion. §  Dementia. §  Coma. §  Seizures. §  Difficulty speaking. §  Tremors and twitching.

 

 

A nutritional approach to treat Neuroinflammation:

 

Recent studies have corroborated the uses of dietary short-chain fatty acids (SCFA) have been able to regulate neuroinflammation and autoimmunity. Therefore, the supplementation of butyrate, propionate, or higher intakes of dietary fiber can initiate an anti-inflammatory response through the actions of regulatory T cells that secrete IL-10.

Glutathione and phytonutrients such as resveratrol and turmeric have been helpful with dampening neuroinflammation. These components have been shown to reduce the inflammation stage and promote the conversion from M1 (activated pro-inflammatory) to M2 (anti-inflammatory phenotype).

Neuroinflammation is a state of chronic inflammation in the brain, but it is like systemic peripheral inflammation. Once the neuroinflammation cascades start, it cannot be stopped or reversed is up to us to manage and control the level of inflammation.

Likewise, peripheral inflammation can permeate the BBB altering the tight junctions, and this can facilitate the passage of pro-inflammatory cytokines to the brain. Thus, it is essential to keep gut inflammation at bay. Therefore, nutritional treatment a major key component for the dampening of neuroinflammation effects. Therefore, supplementation of short-chain fatty acids, glutathione, and turmeric plays a major key in the nutritional treatment of neuroinflammation along with the avoidance of pro-inflammatory foods. – Ana Paola Rodríguez Arciniega. Master in clinical nutrition.

Shabab, Tara, et al. “Neuroinflammation pathways: a general review.” International Journal of Neuroscience 127.7 (2017): 624-633.

Lyman, Monty, et al. “Neuroinflammation: the role and consequences.” Neuroscience research 79 (2014): 1-12.

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