There are more than 600 known brain diseases. Neuroinflammation plays a role in nearly all of them.
And yet, researchers still understand very little about how this common immune response contributes to the development of brain diseases and other neurologic disorders. Complex and unique changes in the body’s immune response underlie nearly every major pediatric, adult, and geriatric neurological and neuropsychiatric disorder. These include Alzheimer’s, Parkinson’s, and Huntington’s diseases, multiple sclerosis (MS), encephalitis, stroke, amyotrophic lateral sclerosis (ALS), schizophrenia, brain tumors, epilepsy, migraines, myopathy and neuropathy, meningitis, chronic pain, and brain disease associated with COVID-19. Together, these diseases affect 60% of the U.S. population and at least 3 billion people worldwide, and they attack the essence of what makes us human: thought, speech, emotion, and movement.
What Exactly Do We Mean by “Inflammation”?
Inflammation is the immune system’s natural response to injury, illness, or infection. For example, if you get a splinter in your finger, you may experience pain, heat, redness, swelling, and irritation in the area as the immune cells do their work to neutralize harmful stimuli—such as foreign bacteria or other infection—and repair tissue. Unpleasant as it may feel at the time, inflammation is a positive healing process.
This healing happens in the brain as well, whether triggered by a pathogen or by direct damage from a physical impact, for example a concussion or a traumatic brain injury (TBI). When tissue in the brain (or spinal cord) becomes inflamed, this is referred to as neuroinflammation. Individuals cannot see or feel the indicators of inflammation inside the brain, as they can with inflammation of the skin. Nevertheless, brain cells are directly affected during a neuroinflammatory response, and a person can experience temporary changes in mental and emotional processes—thinking, concentration, behavior, mood, fatigue, motivation, and so on.
However, if inflammation becomes chronic, lasting or recurring for months or years, it can be a serious concern for patients. In chronic inflammation, the immune system may begin attacking healthy tissue.
How Neuroinflammation Works
While many people think of neurons when they think of brain cells, about 70% of the cells in the central nervous system are a different type, called glial cells. Two important types of glial cells are microglia and reactive astrocytes. These cells help the brain’s immune system. Microglia act like guards, watching for signs of injury or infection. Astrocytes help control blood flow and chemical levels in the brain to create the best conditions for healing.
If the brain’s first immune response doesn’t work—for example, if it can’t get rid of a virus, bacteria, or other threat—glial cells activate a chain of stronger immune responses. This can result in chronic neuroinflammation, meaning the immune system stays activated longer than it should. Over time, this chronic neuroinflammation can start to cause damage to healthy cells, including those of the blood-brain barrier. If the barrier is compromised, foreign pathogens that would normally be blocked can enter the brain—instigating further neuroinflammation, further interfering with brain function, and potentially causing neurodegeneration, or damage to neurons, including those associated with memory.
Chronic Neuroinflammation, Aging, and Neurodegenerative Disorders
While neuroinflammation occurs in all stages of life, it is a cross-cutting mechanism of brain disease and the aging brain. Neuroinflammation is a crucial underlying mechanism that contributes to a wide variety of neurogenerative disorders associated with aging, such as Alzheimer’s and other types of dementia.
“Inflammation causes joints, muscles, the heart, and the brain to age,” explains Dr. David Dodick, Immediate Past Chair of the American Brain Foundation’s Board of Directors. “When the system goes awry or becomes too active, normal brain tissue becomes an innocent bystander. Think of it as ‘inflamm-aging’ — aging caused by inflammation. The connections in your brain get broken. At first you may not notice, but eventually you do.”
Because inflammation has this aging effect on the brain, animal models and clinical trials of new therapies for neurodegenerative diseases have focused on blocking or enhancing inflammatory signal pathways among cells in the central nervous system. These experiments have shown that inflammatory signaling is extremely complex due to many variables, but there is potential for beneficial immune-directed treatments in the future.
Researching Neuroinflammation to “Cure One, Cure Many”
Understanding neuroinflammation is important for neuroscience, the future of treatment, and our concept of how the brain ages. To date, however, there has been no large-scale, coordinated research effort to understand how neuroinflammation affects or leads to brain diseases, such as those associated with aging. This understanding—at the molecular, cellular, and systems levels—is essential to developing medical treatments that act at different points during the progression of a brain disease.
This is why we recently launched our Cure One, Cure Many Award in Neuroinflammation, in collaboration with scientists, disease-specific organizations like the National MS Society and the Encephalitis International, and patient advocacy groups. We are on track to begin awarding millions of dollars in funding for neuroinflammation research projects in 2025.
Humanity should not accept the status quo where so many suffer from brain diseases, injuries, and disorders with the identifiable common denominator of neuroinflammation. A profound understanding of how and when inflammation occurs in the brain and the spinal cord will aid in preventing, detecting, treating, and even curing a broad spectrum of brain diseases.
The American Brain Foundation is committed to finding cures for all brain diseases and disorders. Donate today to make a difference. With your help, we can all experience life without brain disease.