Stroke is not only one of the most common causes of death, but also the most common cause of permanent severe physical disability and cognitive impairment. The brain damage triggers a two-part immune response that leads to localized inflammation in the central nervous system (neuroinflammation) with a parallel suppression of the peripheral immunity. Neuroinflammation can have harmful consequences, but also beneficial effects on regeneration and recovery. Peripheral immunodepression can lead to a weakening of the body's own immune defense and thus to life-threatening infections, especially bacterial pneumonia. These in turn can trigger autoreactive immune responses against brain proteins and thus exacerbate neuroinflammation.

A better understanding of the molecular processes of immune regulation that take place in the body after a stroke should help to develop innovative therapeutic approaches. The Einstein project focussed on small RNA molecules that can be central regulators of inflammatory processes in the brain and in the periphery of the body. The project was based on preliminary work by the two research groups involved, which suggested an important role for cholinergic signalling in the dysregulation of brain-body communication following brain damage.

The basic hypothesis of the project was that specific microRNAs (so-called cholinomiRs) have a regulatory influence on local and systemic immune responses after a stroke via the control of cholinergic genes. Using experimental models and clinical samples from stroke patients, the researchers were able to show that small RNA molecules indeed play an important role in immune regulation after an acute stroke. This leads to a shift in the balance of two subtypes of small RNA molecules in monocytes, which are cells of the innate immunity. While microRNA levels are massively reduced, so-called transfer RNA fragments (tRFs), which influence cholinergic gene regulation specifically, rise strongly. The ‘changing of the guard’ between these small RNA subtypes influences the homeostasis of immune responses after a stroke. The identification of the affected signalling pathways opens up new possibilities for the development of therapeutics and biomarkers at the protein and RNA level