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Even mild inflammation can majorly damage the brain

In both sudden medical emergencies like strokes and chronic conditions such as Alzheimer’s disease, brain inflammation emerges as a critical factor, leading to cognitive decline and even death.

For years, scientists have recognized the lethal potential of severe inflammation on brain cells.

Recent research led by scientists at UC San Francisco sheds light on how even mild inflammation can cause significant damage without directly killing the brain’s neurons.

Inflammation in brain

Traditionally, it was believed that severe inflammation was necessary to destroy brain neurons. However, this new research indicates that even mild inflammation is detrimental.

Instead of killing neurons, it primarily affects the neurites. Neurites are crucial arm-like projections that connect neurons. They are essential for brain functions like learning and memory.

Published in the journal Cell Reports, the findings unveil a previously unknown degenerative pathway caused by inflammation, opening up potential new therapeutic interventions.

“There are several exciting drugs now entering clinical use that interrupt these inflammatory processes, and now we know to look at their effects on neurites,” explained Dr. Raymond Swanson, senior author of the study and a professor of neurology at UCSF with joint appointments at the San Francisco Veterans Affairs Medical Center. Dr. Swanson believes these insights could soon significantly benefit patients.

Inflammation from infection impacts brain health

The body’s immune system responds to injury or infection by initiating inflammation—rushing blood and immune cells to the site, releasing chemicals to combat pathogens. This response is effective against infections but can wreak havoc on the delicate neural networks of the brain.

Consequently, Dr. Swanson’s team focused on how inflammation damages the brain. They were particularly intrigued by molecular aggregates called cofilactin rods (CARs). CARs form after a stroke.

These rods develop when two proteins, cofilin and actin, dissociate. Normally, these proteins support neurites. But in response to a chemical called superoxide, triggered by inflammation, they create disruptive clumps.

Neurite degradation

To further explore this process, the research team induced inflammation in a mouse brain region controlling movement, expecting widespread neuron death and movement issues.

Although the mice exhibited movement difficulties, microscopic examination revealed that it was the neurites, not the neurons, that had deteriorated. This disconnection of neural pathways severely impacted the mice’s motor coordination.

By modifying levels of superoxide or cofilin and treating the brain with inflammatory substances, the researchers were able to reduce CAR formation and neurite damage. Remarkably, this preservation of neurites helped the mice maintain better coordination.

New frontier in neurological disease treatment

This breakthrough provides a clearer understanding of how inflammation contributes to neurological disorders like multiple sclerosis, traumatic brain injury, and amyotrophic lateral sclerosis (ALS).

With this knowledge, scientists can now design interventions to disrupt this inflammatory pathway. Early intervention with anti-inflammatory treatments in stroke patients, for instance, could protect neurites from damage and help preserve cognitive functions.

“Particularly in the aging brain, inflammation can be harmful,” said Dr. Swanson. “By focusing on how neurites are particularly susceptible to inflammation, we may finally be able to gain the upper hand against some of the most prevalent neurological diseases.”

Through this research, we glimpse a hopeful future where targeted treatments could mitigate the subtle yet profound impacts of brain inflammation, preserving vital neural connections and improving the quality of life for those affected by neurological conditions.

Common causes of brain inflammation

Brain inflammation, also known as neuroinflammation, can be triggered by a variety of factors, ranging from infections to lifestyle choices. Here are some common causes:

Infections and brain inflammation

Infections from viruses, bacteria, parasites, or fungi can lead to brain inflammation, known as neuroinflammation. Pathogens such as the herpes simplex virus can cause encephalitis, while bacteria like Neisseria meningitidis can cause meningitis. These infections invade the brain and spinal cord, triggering severe inflammation as the immune system responds aggressively to combat these foreign invaders.

Autoimmune diseases and neurological impact

In autoimmune conditions like multiple sclerosis (MS) and autoimmune encephalitis, the immune system mistakenly attacks the brain or its surrounding structures, causing inflammation. This misguided immune response can damage neurons, the protective myelin sheath, or other parts of the brain and nervous system, leading to various neurological symptoms.

Traumatic brain injury (TBI) and inflammation

Traumatic brain injuries, whether from accidents, sports, or falls, can lead to brain tissue swelling and inflammation. This is part of the body’s repair mechanism but can cause further damage or complications if the inflammation persists, affecting brain function long after the initial injury.

Stroke-induced inflammation

Strokes disrupt blood flow, causing brain cells in the affected area to die and trigger inflammation. The body’s response, which involves sending immune cells and substances to clear out dead cells and debris, can sometimes extend the damage to otherwise healthy tissues.

Toxic exposure and brain health

Environmental toxins like heavy metals (mercury, lead), certain pesticides, and pollutants can cause inflammation in the brain. These substances disrupt the normal function of the nervous system and contribute to the onset of neurodegenerative diseases by triggering inflammatory responses.

Chronic conditions and persistent inflammation

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s involve chronic inflammation. The buildup of abnormal proteins in the brain causes an ongoing inflammatory response, which gradually leads to neuronal damage and disease progression.

Allergic reactions and systemic inflammation

Severe allergic reactions, as seen in conditions like asthma or anaphylaxis, can indirectly affect brain health through systemic inflammation. This widespread inflammatory response can impact the brain and nervous system, exacerbating or initiating neurological issues.

Substance abuse and neuroinflammation

Abusing alcohol, narcotics, and certain medications can lead to both acute and chronic brain inflammation. This inflammation can impair cognitive functions and lead to neurological deficits, exacerbating the harmful effects of the substances themselves.

Diet-induced inflammatory effects on the brain

Diets high in fats, sugars, and processed foods can cause systemic inflammation, including in the brain. This type of diet raises the levels of inflammatory cytokines, which can accelerate neurodegenerative processes and impair cognitive function.

Stress and Its Impact on Brain Inflammation

Chronic stress releases cortisol, a hormone that regulates inflammation. Prolonged elevated cortisol levels can increase inflammation throughout the body, including the brain. This can affect mood, behavior, and cognitive functions, highlighting the need to manage stress effectively to maintain brain health.

The study is published in the journal Cell Reports.


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