discovered some white blood cells that aggravate the damage – time.news

2023-05-15 17:13:47

Of Health editorial

Researchers at San Raffaele in Milan have identified a subpopulation of “neutrophils” involved in the aggravation of the consequences of the event

Some specific white blood cells would be implicated in the aggravation of the damage induced by ischemic cerebral stroke. This was identified by researchers at the San Raffaele Hospital in Milan, coordinated by Marco Bacigaluppi, of the Neuroimmunology Research Unit, directed by Professor Gianvito Martino, who published the results of their study in the journal Nature Immunology. The research compared ischemic stroke in mouse models (i.e. laboratory mice) of different ages, describing for the first time, thanks to molecular imaging and genomics technologiesthe presence in aged animals of a subpopulation of neutrophil granulocytes
(a type of white blood cell) immature and harmful. Released early from the bone marrow, due to their immaturity, these cells in the aged mouse they accumulate in the affected cerebral area becoming capable of aggravating the damage induced by ischemia, i.e. by the lack of blood supply caused by an obstruction of the vessels, with consequent worse disability and mortality.

Perspectives

The discovery of this alteration in the immune response, defined by the researchers abnormal granulopoiesisrepresents a contribution to understanding the consequences of ischemic cerebral stroke and, identifying new potential therapeutic targets, paves the way for the development of new therapies for this disease. Concrete possibility also because the researchers compared the results obtained in the laboratory with blood samples of adults and elderly people affected by stroke, hospitalized in the Stroke Unit of the San Raffaele Hospital. Even in these patients, and particularly in those of an older age, the presence of an abnormal granulopoiesis was highlighted, similar to that found in the elder mouse. «Recently the San Raffaele Hospital launched a multi-year strategic biomedical research program within which the area aimed at studying aging plays a prominent role. Combining research and clinical experiences we aim to understand in greater detail not only the mechanisms related to aging but also how these mechanisms can favor or even determine the onset of many serious diseases including cerebrovascular and neurodegenerative diseases. This result is one of the concrete fruits of this program because, not only starting from experimental observation, it draws the basis for developing new and more effective therapeutic strategies, but also because it gives us a glimpse of one of the possible ways forward to guarantee an advance in the years in good health and free from disease,” explained Gianvito Martino.

Premises and method

Previous studies have described the worst outcome in terms of disability and mortality after cerebral ischemia in elderly animals and greater disability also present in elderly patients with ischemia. “Just as 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 the ability of the bone marrow to produce fewer lymphocytes and more neutrophils, but today with this work we have understood the cause and the mechanism» Marco Bacigaluppi pointed out. The researchers therefore, starting from clinical observation, studied in the laboratory the different inflammatory response that is generated after ischemia within the brain tissue of old and young mice and, using single cell transcriptomic technologies and multicolor high definition, in collaboration with national and international research groups, were able to characterize the increase in older mice of specific subpopulations of immature neutrophils with pro-inflammatory and pro-thrombotic characteristics.

What are neutrophils for?

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 one 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 make damage worse. In the event of an ischemic stroke, they are called to the site of the brain damage as an emergency to do their duty. In the elderly individual, however, they fail to complete the maturation in the marrow and migrating immature they tend to accumulate in excess in the site of the damage causing a worsening of the cerebral microcirculation (worse reperfusion) and consequently an aggravation of the stroke. With a counter-test, they “rejuvenated” the bone marrow of older mice – before cerebral ischemia – and saw that this procedure was able to restore normal granulopoiesis, improving the outcome of the stroke. The objective “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”. explains Bacigaluppi. The target of future studies, and already partly in progress, will be that of 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, which worldwide represent the second cause of death and one of the main causes of disability. In Italy there are about 185,000 people affected by stroke every year.

May 15, 2023 (change May 15, 2023 | 17:12)

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