In another study of bowel conditions associated with brain diseases, scientists have linked bacterial colonies that are located at the base of the cause of common blood-vessel abnormalities in the brain.
These malformations can cause paralysis called cerebral cavernous malformations (CCMs). This does not leave much choice except surgery. If there is no operation, nothing can be done from the palliative-palliative care. However, to determine what causes these abnormalities, maybe they can be a means of preventing them before they come to the table.
An international team led by researchers from the University of Pennsylvania is working on genetically engineered mice that are prone to develop vascular lesions.
Previous research shows that this hereditary state may be due to mutations that destroy certain genes. These genes suppress the major, important signals that normally affect the development of brain cells that make up blood vessel walls.
Although this discovery provides a way to identify those at risk of developing CCM, there is unfortunately no drug available to replace missing genes, and therefore nothing much can be done.
However, since CCM differs significantly in individuals with this mutation, it may be necessary to go further than a few fractures.
Studies on mice
By studying a few generations of genetically-produced mouse populations, researchers have discovered individuals who seem to be resistant to developing lesions, although they still have one of the CCM mutations.
While the majority of mice in this population are resistant, several infant malformations develop. These pups develop abseler in the abdominal region due to the injections they have taken during the research, which could indicate a potential cause.
To test whether these infections play a role in the development of CCM, 16 "resistant" mice are inoculated with one gram of live negative bacteria, normally called Bacteroides fragilis, in the intestine. 9 of these mice continue to develop vascular lesions and their spleens become inflamed and apselenic and the bacteria also appear to influence the growth of cells that cover the blood vessels of the brain from the site of infection. Generally, gram-negative bacteria such as B. fragilis affect cell responses of mammals such as humans and mice through a molecule in the outer membrane called lipopolysaccharide (LPS) or endotoxin.
The research team injects the endotoxin from the bacteria into the normal, and especially not produced, mice, along with the mutated strain-born mice to understand whether this molecule is causing malfromation in particular.
As suspected, those with a fractured gene that is susceptible to CCM develop vascular lesions in their brains, whereas genes with functional versions in mice do not.
Called "blood brain barrier", cells that cover blood vessels usually prevent toxic substances such as endotoxin and bacterial cells from entering our central nervous system.
How the endotoxins affect these cells is a secret ...
Jaesung Peter Choi, of the University of Sydney in Australia, told Science Alert that this problem should be investigated and says: "But we think that CCM formation is driven by the activation of the blood-brain barrier by the immune receptors in the lumen and blood side of the blood-brain barrier."
When these immune receptors, termed TLR4, are activated by an endotoxin, blood-brain barrier cells become abnormal growth. Related genes usually prevent this malfromation, but in mice with the mutated version, this process can not stop anything.
Importantly, differences in the TRL4 immune receptor in humans may be responsible for some of the differences and changes in the situation in people with CCM mutations.
The comparison of CCM susceptible mice grown in germ-free conditions and CCM susceptible mice produced in less sterile conditions shows that bacterial circulation plays a crucial role in transforming only one mutation into a fatal disease.
Researchers suggest that instead of focusing on TRL4 immune receptor-targeted therapies, they focus on the intestinal microbiota.
"The manipulation of intestinal microbiome-host interactions is a more exciting potential strategy for the treatment of a lifelong disease like CCM," the research team writes.
Researchers raise a few generations of mice that have been taking antibiotics to their mothers to test whether they will use antibiotics to affect lesion development in mutant mice, and look at the number of bacteria on each colonic lesion and gut.
Just as they found in germ-free rats, a 96% reduction in bacteria overlaps with a similar decline in lesions.
Destroying our immune system with antibiotics may not be an open and direct solution, and we must keep in mind the potential differences between mice and humans.
We are still learning the complexity of our microbiota and the numerous health conditions associated with the diversity of microorganisms in our digestive system ...
However, this research is a major step forward in order to open up new ways of preventing sensitive lesions in a situation where there is now little treatment.
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