In an ischaemic stroke, the blood supply to the brain is interrupted. This triggers a dangerous chain reaction: blood vessels in the brain change, inflammatory processes occur, and the interaction between nerve cells, blood vessels, and the cells that support them in the brain – the neurovascular unit – is disrupted. As a result, nerve cells gradually die off. Despite intensive research, it is still unclear how these processes are linked.

A new project at the 威尼斯赌博游戏_威尼斯赌博app-【官网】 of Augsburg titled “Ischemia-induced impairments of the neurovascular unit” (Isch?mie-bedingte Beeintr?chtigungen der neurovaskul?ren Einheit) is researching these processes. It is funded by the German Research Foundation (DFG) until the beginning of 2029.

Cells in a state of emergency

The research being conducted by Prof Anja Meissner, professor of physiology and vascular biology at the Institute of Theoretical 威尼斯赌博游戏_威尼斯赌博app-【官网】icine, and her team could help to develop new therapeutic approaches. Due to many unknown factors, treatment for ischemic stroke has so far been limited to restoring blood flow to the damaged areas of the brain. However, researchers hope that once the changes in the brain are better understood, new treatment options will become available.

The project focuses on the molecule sphingosine-1-phosphate (S1P) and, in particular, its receptor S1PR3. The molecule S1P is important for blood vessel health and the body’s immune response. It can bind to specific structures on cells called S1P receptors. These can have a positive effect on blood circulation in the brain. Previous research by Meissner and her team has shown that one of the receptors, S1PR3, is highly activated after a stroke.

Helpful or harmful?

How this activation influences damage to the brain has, however, been unclear until now. “Does it have a protective or harmful effect? Can this signalling pathway be influenced therapeutically? That’s what we want to find out,” says Meissner. “To do this, we are investigating exactly how and when S1PR3 becomes active in different cell types.”

The S1PR3 receptor is mainly found in astrocytes, cells that are crucial for the functioning of the neurovascular unit, as they functionally link blood vessels and nerve cells, for example. However, S1PR3 is also found in blood vessel cells, where it is also strongly activated.

Starting point for new therapies

It is conceivable that this activation is partly part of the clinical picture, but also partly a protective mechanism. It helps to form a shell around the dead tissue. This is important because this necrotic core is toxic to the surrounding tissue. However, the scar tissue can later hinder the reconstruction of neural connections and thus slow down recovery.

“It could be useful to control the increase in S1PR3, that is, to promote it at certain times and suppress it at others,” explains Meissner. “If we can figure this out, it could help in the long term to significantly reduce brain damage after a stroke and improve the chances of recovery for those affected.”

Determining the outcome of a stroke

To analyse these mechanisms, the research team is using innovative mouse and cell culture models. By combining both models, the complex processes can be studied in detail, both in living organisms and in complex cell culture models that can replicate the behaviour of different cells in the neurovascular unit after a stroke. This allows the specific communication at the cellular level to be investigated.

In addition to potential therapies, Meissner’s team’s research also focuses on determining the outcome of ischemic strokes. “The activation of the S1PR3 receptor could potentially be used as a diagnostic marker,” explains Meissner. However, there is still a long way to go before this becomes a reality. But Meissner is confident: “As researchers, we hope that the results of our research can one day be transferred to clinical practice and ultimately benefit patients.”

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