Week 13:  Inflammation and the brain

We all know about inflammation.  That moment when you land wrong, and you look down as your ankle starts to swell.  Or it is that arthritic knee that swells and causes pain.  That is inflammation, and it is pretty noticeable.  But there is inflammation that occurs which is not so noticeable, and which can be far more dangerous.  This type of inflammation is a long term response, affecting the immune cells and internal organs.  This lesson will focus on chronic inflammation, how it occurs, what happens in the brain, and what we can do about it.   

Inflammation is our body’s way of protecting itself when something harmful happens.  It allows your body to heal and get back to normal.  If something damages your tissues (like a sprained ankle), your body releases chemicals that cause the immune system to react, fighting off germs and start the healing process.  Signs of inflammation, such as redness, swelling and warmth are signs that your body is working to fend off infections and repair itself.  Inflammation can be acute or chronic:

·         Acute inflammation:  This would be seen in a short duration, from a few hours to a few days.  Symptoms appear quickly, and the body returns to its original state when the symptoms recede. Inflammation is usually seen at the site of the injury or infection. Acute inflammation is a necessary part of healing.

·         Chronic inflammation: Chronic inflammation occurs when the inflammation continues over a long period of time.  It is not always protective or beneficial.  It is a long-term and persistent immune response which can last for months or years, often to tissue damage and various health issues.  It is also linked to a number of chronic diseases including heart disease, diabetes, obesity, autoimmune diseases, neurodegenerative diseases, chronic kidney disease and some cancers.

·         Diseases causing inflammation: There are diseases that cause inflammation as well.  These diseases often end in “itis”.  They can include cystitis (inflammation of the bladder), bronchitis (inflammation of the bronchi), otitis media (inflammation of the middle ear) and dermatitis (inflammation of the skin).

Some of the primary causes of chronic inflammation include:

• Untreated causes of acute inflammation:  This can include lingering infections (bacterial, viral) which cause a persistent low-grade inflammatory state.  Or it can include injuries that have not fully healed.

• Autoimmune disorders:  In these conditions, the immune system becomes confused and starts treating healthy tissues as threats, which lead to continuous inflammation.  Some examples include rheumatoid arthritis, lupus, inflammatory bowel disease and psoriasis.

• Long term exposure to irritants:  With consistent exposure to certain substances, the body can become irritated, resulting in a state of chronic inflammation.  Examples include industrial chemicals, polluted air or allergens

• Lifestyle:  Although most of the above causes cannot be controlled easily, lifestyle can significantly contribute to chronic inflammation.  Some of the lifestyle choices which can be modified include:

o Obesity (fat tissues release inflammatory substances)

o Unhealthy diet (highly processed foods, added sugars, trans fats and refined carbohydrates can fuel inflammation)

o Lack of exercise (physical inactivity increases inflammatory markers)

o Smoking (smoking introduces toxins and irritants into the body, triggering an inflammatory response)

o Chronic stress (stress hormones can disrupt immune system regulation, leading to increased inflammation)

o Poor sleep (interrupted or inadequate sleep is linked to higher inflammation levels)

• Unexplained causes:  Sometimes, the root cause remains elusive, even after comprehensive testing

In addition to these factors, there are a couple of other things to consider.  As we age, the risk of chronic inflammation naturally increases.  In addition, some individuals may have a genetic predisposition.  And keep in mind that inflammation often stems from many factors, rather than just a single cause.

Side note: Conditions of the immune system (Elmer, 2018)

There are conditions where the immune system attacks the body’s own cells by mistake, resulting in inflammation.  These include rheumatoid arthritis, inflammatory bowel disease, psoriasis and multiple sclerosis.

• With rheumatoid arthritis, your immune system attacks your joints, leading to symptoms like joint pain, swelling and stiffness, fatigue, numbness and tingling and a limited range of motion.

• In inflammatory bowel disease, inflammation occurs in the digestive track.  Symptoms can include diarrhea, stomach pain, cramping or bloating, weight loss and bleeding ulcers.

• Psoriasis is a chronic skin disease that speeds up the life cycle of skin cells, causing cells to build up rapidly on the surface of the skin.  This results in scaly and red patches which can be itchy and painful.

• With multiple sclerosis, your body attacks the myelin sheath, the protective covering of nerve cells.  You might experience symptoms such as numbness and tingling of the arms, legs or one side of the face, balance problems, double vision, blurry vision or partial vision loss, fatigue and cognitive problems like brain fog.

Many factors can lead to inflammation, such as chronic or acute conditions, some medications and exposure to irritants or materials your body cannot easily eliminate.  If there are recurrent episodes of acute inflammation, you might develop a chronic inflammatory response.

If you suspect that you might have chronic inflammation, your best bet would be to visit your healthcare provider.  Here are some of the ways that they can determine if you have this condition:

• Medical history and physical examination:  They will consider your medical history, previous infections, chronic diseases or any factors which might result in chronic inflammation.  They will also look for signs of inflammation such as swelling, redness or pain.

• Blood tests:  Blood tests can be used, including those that measure biomarkers associated with inflammation.  They can include:

o C-reactive protein (CRP), a protein produced by the liver in response to inflammation.  High levels might suggest chronic inflammation.

o Erythrocyte sedimentation rate (ESR), the rate at which red blood cells settle at the bottom of a test tube.  Increased ESR might suggest chronic inflammation. The quicker they sink, the more likely you are to be experiencing inflammation.  It does not pinpoint specific causes of inflammation, just tells your doctor if inflammation is occurring.

o Measuring the level of pro-inflammatory cytokines such as IL-6 and TNF-alpha)

o Serum protein electrophoresis, (SPE) is considered the best way to confirm chronic inflammation.  It measures proteins in the liquid part of the body to identify issues.  

o Fibrinogen may also be measured in blood tests.  A higher amount may mark inflammation, although that is not a standard test.

o Plasma viscosity measures the thickness of blood.  Inflammation or infection can thicken plasma.

• Imaging studies such as X-rays, magnetic resonance imaging (MRI) or ultrasound can visualize the areas of inflammation especially in cases of joint inflammation or localized inflammatory conditions. 

Neuroinflammation refers specifically to inflammation within the nervous system, particularly the brain and spinal cord. It's a complex process similar to chronic inflammation, but it occurs in the highly specialized environment of the central nervous system (CNS).

Unlike chronic inflammation that can occur anywhere in the body and is related to triggers like infections, autoimmune disorders or lifestyle choices, neuroinflammation is a specialized type of chronic inflammation occurring within the CNS.  The CNS has a unique immune system shielded by the blood-brain barrier, which makes neuroinflammation distinct. 

How does this happen?  The blood-brain barrier is a tightly controlled layer of cells that protects the delicate environment of the brain from toxins and pathogens in the bloodstream. In neuroinflammation, this barrier gets compromised. It becomes leaky, allowing immune cells and inflammatory substances that normally wouldn't cross to enter the brain. These substances then trigger even more inflammation within the brain itself, leading to damage and impacting the way brain cells function. 

While the exact mechanisms are still being researched, chronic neuroinflammation is strongly linked to the development and progression of various neuropsychiatric disorders. Here's how it might contribute:

• Damage to brain cells: Neuroinflammation can cause the release of toxic chemicals that damage and kill neurons (brain cells) and disrupt communication between them.

• Disrupted neurotransmitters: Inflammatory processes can alter the production or function of neurotransmitters, essential chemical messengers in the brain that regulate mood, memory, and thinking.

• Reduced neurogenesis: Chronic inflammation might impair the brain's ability to generate new neurons, which is crucial for learning and memory.

Examples of Neuropsychiatric Disorders Linked to Neuroinflammation:  (Najjar, 2013) (Hong, 2016) (Asslih, 2021)

• Alzheimer's Disease: Protein buildup in the brain associated with Alzheimer's triggers inflammatory responses that contribute to neuronal damage and cognitive decline.

• Parkinson's Disease: Neuroinflammation is observed in the areas of the brain affected by Parkinson's, potentially playing a role in the degeneration of dopamine-producing neurons.

• Depression: Studies suggest that chronic inflammation might be involved in some cases of depression, impacting mood regulation pathways in the brain.

• Multiple Sclerosis (MS): An autoimmune disease where the immune system attacks the myelin sheath protecting nerve fibers. Neuroinflammation is a key aspect of MS and contributes to nerve damage and disability.

Eat these foods to fight inflammation:    Anti-inflammatory diets have been popular for many years and include foods that are typical of a Mediterranean diet.  Of particular benefit are foods such as berries, fatty fish, broccoli, avocados, green tea, mushrooms, spices (like turmeric, ginger and clove), tomatoes, olive oil, leafy greens and nuts.  Red wine in moderate amounts may be helpful. Other options include mung bean (herbal medicine known for its anti-inflammatory effects) and micronutrients such as magnesium, vitamin D, vitamin E, zinc and selenium).  You may also benefit from sesame oil, which is known for its potential hypotensive activity.

Avoid these foods if you have inflammation:  There are also certain types of food that can cause or worsen inflammation.  If you are experiencing inflammation, it would be helpful to limit foods such as red meats, refined carbohydrates (like white bread and pastries), fried foods and processed meat.