Stroke, discovered the mechanism in the brain that makes it more serious
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“Abnormal Granulopoiesis”. Mark these two words. The terms in practice indicate an improper production of white blood cells by the bone marrow of neutrophils, particular white blood cells, immature. These cells, released right from the blood production plant, due to their immaturity would act as “fuel” for the damage induced by the cerebral ischemia that led to the stroke.
Result: if these cells accumulate, there is a substantial worsening of the situation. To reveal this mechanism, among other things opening the way to perspectives of therapy aimed precisely at this cellular target, is a research that appeared in Nature Immunologyconducted by doctors and researchers of the Irccs San Raffaele Hospital in Milan, coordinated by Marco Bacigaluppiof the Neuroimmunology Research Unit, under the direction of Gianvito Martinoscientific director and pro-rector for Research and the Third Mission of the Vita-Salute San Raffaele University.
The research went to evaluate what happens in the case of ischemic stroke (ischemia is the most frequent cause of stroke, and occurs in about four out of five cases of brain lesions of this type) in the brain of elderly mice.
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The confirmations in the blood of patients
The study described for the first time, thanks to the use of sophisticated technologies of imaging molecular and genomics, the presence in the elderly mouse of a subpopulation of neutrophils, cells that are part of the white blood cells, which appears to be immature and consequently harmful. Released early from the bone marrow, due to their immaturity, these cells, in the elderly mouse, accumulate in excess in the affected brain area, becoming capable of aggravating the ischemic damage, with consequent worse disability and mortality. But there’s more: in addition to the classic experimental observation, in the laboratory, the scholars also wanted to see if something similar also happened in flesh and blood patients.
So they compared the results obtained in the laboratory with blood samples of adults and elderly people affected by stroke, hospitalized in the Stroke unit (i.e. the intensive care unit in case of stroke) of the San Raffaele Hospital. Also in these patients, and in particular in those of an older age, the presence of an abnormal granulopoiesis was highlighted, similar to that found in the elderly mice.
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The prospects for the future
Old men and old rats, somehow, may have a common path in case of ischemic stroke, in terms of disability and outcomes. According to Bacigaluppi, “just like in humans, disability in mice after cerebral ischemia increases with age and there is greater mortality and difficulty in recovery. We also knew that aging causes alterations in the immune system, in particular of the ability of the bone marrow to produce fewer lymphocytes and more neutrophils, but today with this work we understand the cause and the mechanism”.
The objective of future studies, which are already partly underway, will therefore be to develop specific molecules which, by interfering with the identified molecular mechanisms, can normalize the abnormal granulopoiesis. The ultimate goal is to develop new therapeutic strategies that can be effective in cerebrovascular diseases. “This and further molecular and functional studies on neutrophil differentiation will pave the way for the development of effective and selective approaches to rebalance the granulopoiesis that occurs in the elderly population in order to promptly interfere with the onset of pathogenic subsets of neutrophils – concludes Bacigaluppi”.
To understand how this could be a therapeutic target for the future, just think that with a counter-test, the scholars have “rejuvenated” the bone marrow of older mice – before cerebral ischemia. And they noted that the procedure was able to restore normal granulopoiesis, improving stroke outcome.
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What are neutrophil white blood cells
Neutrophils are a heterogeneous population of immune system cells produced by the bone marrow. Once mature, they migrate into the blood system ready to carry out their action against foreign agents, especially infectious ones, to preserve the biological integrity of the organism.
It is now known that neutrophils are a heterogeneous population of white blood cells with multiple and different functions: they can play a fundamental role in fighting infections but in some specific situations they can also worsen damage. In the event of an ischemic stroke, these cells are called to the site of brain damage in an emergency to do their job.
In the elderly individual, however, they are unable to complete the maturation in the marrow and migrating immature tend to accumulate in excess in the site of the damage causing a worsening of the cerebral microcirculation, therefore with less blood flow also through circles that the system puts in place to compensate for the damage and consequently an aggravation of the stroke.
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