Chronic stress and inflammation in the brain can cause multi-organ dysfunction including severe gut failure, mediated by a newly identified nerve pathway in animal models of multiple sclerosis (MS), a Japanese study shows.
The discovery of this underlying mechanism of MS is described in the study, “Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit,” which appeared in the journal eLife.
MS is an autoimmune disease caused by CD4+ T-cells that cross the blood-brain barrier protecting the central nervous system. This inflames and stresses the brain and spinal cord.
In previous studies, a team led by professor Masaaki Murakami of Japan’s Hokkaido University showed that these cells could cross the blood-brain barrier in specific sites. These entrance sites depend on brain regional activation, which was found to be triggered by specific nerve interactions — a mechanism the team called gateway reflexes.
In collaboration with other Japanese researchers and a team from Germany, the project aimed to address the potential correlation among chronic stress, brain inflammation and organ failures in MS.
Using mice with MS-like disease — the experimental autoimmune encephalomyelitis model — researchers found that animals that had autoreactive CD4+ T-cells and which were exposed to stressful conditions developed severe symptoms such as gastrointestinal failure, or even death.
Detailed analysis of the animals’ brains showed that in stressed mice, CD4+ T-cells accumulated in two specific sites in the center of the brain around blood vessels. This event would cause inflammation around those vessels, and activation of a nerve pathway that is commonly turned off. This switch led to gut dysfunction, bleeding and failure.
“These results demonstrate a direct link between brain micro-inflammation and fatal gastrointestinal diseases via the establishment of a new neural pathway under stress,” Murakami, the study’s senior author, said in a news release.