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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, a Japanese study shows.
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.
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.
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.
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.
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.
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.
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.
Researchers were able to prevent gut symptoms by inhibiting
inflammation in the brain or blocking the nerve pathway responsible for driving
the signals from the brain to the gastrointestinal tract.
inflammation in the brain or blocking the nerve pathway responsible for driving
the signals from the brain to the gastrointestinal tract.
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