How Does Systemic Inflammation in the Body Cause Neuroinflammation in the Brain?
The chronic inflammation of aging is harmful, disruptive of tissue structure and function, altering cell behavior for the worse. The immune system reacts to many of the varied signs of molecular damage that become prevalent in old tissues, such as DNA debris from dying cells, and the result is unresolved inflammatory signaling. Neurodegenerative conditions in particular appear to be driven by inflammation, but given that the brain is separated from the body by the blood-brain barrier, and the immune systems of brain and body are also distinct and separate, how is it that inflammation in the body generates neuroinflammation in the brain? Researchers here discuss what is known of the mechanisms involved.
Inflammation in the brain has drawn widespread attention due to its implication in several diseases at multiple stages of life. For instance, some studies have suggested a relationship between neuroinflammation and several types of dementia. Several insults can cause neuroinflammation, such as viral infection in the central nervous system, peripheral inflammation such as chronic joint pain and gut inflammation, and autoimmune issues. In patients with specific types of cancer, such as small cell lung cancer, the immune system cross-reacts with distinct antigens to cause damage to neural tissue and trigger neuroinflammation.
Taken together, persistent systemic inflammation increases the likelihood of neuroinflammation. Meanwhile, factors such as lifestyle also contribute to neuroinflammation. Unhealthy eating habits have been shown to influence the balance of intestinal microbiota, change the blood-brain barrier (BBB) permeability, and cause neuroinflammation. Moreover, mental stress has been shown to increase the levels of several cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) to trigger neuroinflammation. Among the known causes of neuroinflammation, the influence of systemic inflammation on neuroinflammation has scarcely been explored. Recent evidence suggests that chronic peripheral inflammation causes systemic inflammation which may enhance the synthesis of pro-inflammatory cytokines and other inflammation-promoting mediators, activating neuroinflammation in the diseased brain.
Some studies have pointed out the relationship between systemic inflammation and microglial activation via multiple neurotoxic factors, including TNF-α, IL-1, and ROS. Microglia activation is the principal driver of inflammation in the brain. It has been suggested that chronic inflammation breaks down the BBB, degrading the separation of central and peripheral circulation system, leaving the central nervous system (CNS) vulnerable. The close bidirectional relationship of the gut-brain axis, which includes neural, hormonal, and immune communication also plays a vital role in neuroinflammation caused by systemic inflammation. Thus, the persistence of peripheral inflammation causes systemic inflammation and the enhancement of pro-inflammatory factors and disruption of the brain tissue protection, all lead to neuroinflammation.