Scientists at Sechenov University have established that neuroinflammation – a key process determining the extent of brain damage in ischaemic stroke – unfolds differently depending on patient age. These differences may affect disease progression and treatment efficacy, and should therefore be taken into account when developing new therapies. The findings were published in the International Journal of Molecular Sciences.
Ischaemic stroke occurs when a blood vessel becomes blocked, leading to brain tissue death due to oxygen deprivation. However, a significant portion of damage develops after this event – as a result of neuroinflammation, the body’s immune response to ischaemia. Dysregulation of this process causes secondary damage to neural tissue and largely determines the severity of the patient’s condition and the effectiveness of subsequent recovery.
In the study, scientists analysed brain tissue samples from 184 patients aged 18 to 74 who had died from ischaemic stroke or other causes. Patients were divided into three age groups: young (18–44), middle-aged (45–59) and elderly (60–74). Comprehensive analysis – from histological to molecular – allowed them to track how the inflammatory response in the penumbra – the region surrounding the core lesion – changed in the first days after stroke.
In younger patients, the early immune response was driven primarily by innate immunity cells – natural killer (NK) cells and NKT cells. These cells rapidly migrated to the damaged area, shaping the inflammatory response and triggering timely repair mechanisms. Moreover, younger patients showed better preservation of viable neurons, active neoangiogenesis and a more pronounced shift of immune cells towards a cytoprotective, repair-promoting phenotype. This indicates a higher reparative potential of the brain at a younger age.
In elderly patients, the picture was different. T-lymphocytes predominated in the lesion, while NK-cell activity dropped sharply. At the same time, a pronounced pro-inflammatory background persisted: oxidative stress intensified, neuronal death progressed, and the transition from inflammation to the reparative stage was significantly impaired.
“Our study identified age-related differences in the local inflammatory response. In older patients, coordination between vascular and immune components is impaired, and repair mechanisms are activated much more weakly, which ultimately affects recovery after ischaemic stroke. These findings are important not only for understanding the pathogenesis of brain damage but also for identifying new diagnostic and prognostic markers of ischaemic stroke,” said Tatiana Demura, director of the Institute of Clinical Morphology and Digital Pathology.
Morphological analysis also showed that with age, changes related to depletion of neuronal and vascular resources accumulate in brain tissue: the number of neurons decreases, microvessel condition deteriorates, and angiogenic activity and tissue repair capacity decline. These processes create an additional backdrop that exacerbates stroke damage.
“We observed that in young patients, innate immunity cells – NK and NKT cells – play a key role in the early response. They rapidly migrate to the injury site, determining the subsequent pattern of inflammation and timely activation of nerve tissue repair mechanisms. In elderly patients, the picture was different: due to an imbalance of inflammatory cytokines, T-lymphocytes predominated in the lesion, while NK-cell activity sharply declined. This contributed to prolonged oxidative stress, progressive neuronal death and dysregulated neuroinflammation, with no clear transition to the reparative stage,” said Grigory Demyashkin, head of the Histology and Immunohistochemistry Laboratory at the Institute of Translational Medicine and Biotechnology. “This means that therapeutic strategies developed without considering age may work differently in different patient groups. In the future, this opens up possibilities for more precise selection of anti-inflammatory and neuroprotective therapies.”
According to the study authors, it is too early to revise existing stroke treatment protocols, but the results show that patient age and immune profile should be considered separately when developing new drugs and designing clinical trials. Some of the immune markers studied could potentially be measured during life – for example, in blood tests. In the future, this approach could help more accurately predict stroke severity, assess the risk of complications and select more personalised therapy.
