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Neuro into the network: new data on brain inflammation will help recovery after stroke
Age is one of the key factors influencing the development of inflammatory processes in the brain after a stroke, Russian researchers have found. Analysis of patients' tissues showed that the immune response in young and elderly people differs significantly at the cellular level, which means that therapy should be more targeted. The results obtained will help make a breakthrough in the personalized treatment of cerebral ischemia and create new drugs. In addition, understanding the basic mechanisms of inflammation will help in creating methods that can reduce the amount of damage to nervous tissue due to stroke, experts told Izvestia. However, in order to definitively confirm the identified patterns, it is necessary to study larger groups of patients and further verify the results in clinical settings.
Brain inflammation depends on age
Scientists at Sechenov University have found that neuroinflammation, one of the key processes that determine the extent of brain damage in ischemic stroke, proceeds differently depending on the patient's age. These differences can affect the course of the disease and the effectiveness of therapy, which means that they should be taken into account when developing new treatment methods.
Ischemic stroke occurs due to blockage of a vessel and death of brain tissue due to lack of oxygen. However, a significant part of the damage develops after that — as a result of neuroinflammation, that is, the body's immune response to ischemia. It is the dysregulation of this process that leads to secondary damage to the nervous tissue and largely determines the severity of the patient's condition and the effectiveness of further recovery.
In the study, the researchers analyzed brain tissue samples from 184 people who died due to ischemic stroke or other causes. The patients were divided into three age groups: young (18-44 years old), middle-aged (45-59 years old) and elderly (60-74 years old). A comprehensive analysis, from histological to molecular— made it possible to trace how the inflammatory response in the penumbra area, the area around the main lesion, changes in the first days after a stroke.
It turned out that in young patients, innate immune cells, natural killer cells (NK cells) and NKT cells, play a key role in the early immune response. They quickly migrate to the area of damage, determining the nature of inflammation and the timely launch of recovery mechanisms.
In elderly patients, the picture turned out to be different: T-lymphocytes prevailed in the lesion, while the activity of NK cells decreased sharply. At the same time, a pronounced pro-inflammatory background persisted: oxidative stress increased, neuron death progressed, and the transition of inflammation to the recovery stage was much worse.
— The study revealed age-related differences in the local inflammatory response in patients. Thus, in the older age group, coordination between vascular and immune components is disrupted, and the repair mechanisms are triggered much more weakly, which will eventually affect the recovery of patients who have suffered an ischemic stroke. The data obtained are important not only for understanding the pathogenesis of brain damage itself, but also for searching for new diagnostic and prognostic markers of ischemic stroke," said Tatiana Demura, Professor, Director of the Institute of Clinical Morphology and Digital Pathology.
Morphological analysis also showed that with age, changes in brain tissue associated with depletion of neuronal and vascular resources increase: the number of neurons decreases, the condition of microvessels worsens, angiogenic activity and the tissue's ability to repair decrease. These processes create an additional background that enhances the damage caused by a stroke.
"This means that age—neutral therapeutic strategies may work differently in different patient groups. In the future, this opens up opportunities for a more accurate selection of anti—inflammatory and neuroprotective therapies," said Grigory Demyashkin, Professor, Head of the Laboratory of Histology and Immunohistochemistry at the Institute of Translational Medicine and Biotechnology at Sechenov University.
According to the authors, it is too early to talk about reviewing existing stroke treatment regimens. However, the results show that when developing new drugs and conducting clinical trials, the age of patients and their immune profile must be taken into account separately. This will help to more accurately predict the severity of a stroke and assess the risk of complications.
How to use the data obtained in the treatment of strokes
The age-related differences in the cellular composition of the local inflammatory response in ischemic stroke are of fundamental importance for understanding the pathogenesis of secondary brain damage, Alexander Zakharov, director of the Research Institute of Neuroscience at the SamSMU of the Russian Ministry of Health, PhD, associate professor, market expert at NTI Helsnet, told Izvestia.
— The data obtained substantiate the need for age stratification in clinical trials of neuroprotective and anti-inflammatory drugs, and also allow us to reconsider the role of immune mechanisms as predictive biomarkers of stroke severity and recovery potential. In clinical practice, the results can be used to develop age-appropriate therapeutic strategies," the specialist said.
Inflammation is once again becoming the main topic for study in various age-related diseases, Alexander Karasev, a doctor, a member of the Federation of Laboratory Medicine of the Russian Federation, and an expert on the Neuronet market, told Izvestia. According to worldwide research, the level of inflammatory biomarkers can determine the severity of a stroke and serves as a reliable prognosis of a patient's recovery, he noted.
— The discovery of the main mechanisms of inflammation and the subsequent development of approaches to the proper management of this process, that is, stopping inflammation at the right moment, can remove a significant part of the brain damage due to stroke. And the assessment of changes in the biomarkers of these processes allows us to determine the prognosis in advance," the specialist said.
However, the research needs to be continued in order to confirm the identified patterns in a larger cohort of patients, the doctors noted. The results of the study are published in the International Journal of Molecular Sciences.
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