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Cell-specific Biomarkers in the Blood Reflect What Happens in the Brain During Stroke

group photo of Andreas Enström, Gesine Paul-Visse and Arne G. Lindgren. photo.
Three of the Lund University researchers that studied the brain environment of patients during an ongoing stroke. From left: Andreas Enström, Gesine Paul-Visse and Arne G. Lindgren. Photo: Ingemar Hultquist.

By analysing small microvesicles that cells release to communicate with their surroundings in the blood, researchers at Lund University map what happens in the brains of stroke patients. The study published in the scientific journal Stroke expands our understanding of stroke and opens doors to new treatment strategies.


Ischemic stroke, caused by a blood clot in the brain, is the leading cause of death and disability worldwide. Currently, treatment options in the acute phase of a stroke are limited to only one type of medication, which must be administered quickly, that is within a few hours of the onset of stroke symptoms.

One of the challenges in the quest for new treatments that can be given beyond this narrow time window is the difficulty in studying the specific response of different brain cells during  stroke. However, researchers at Lund University have now found an innovative way to decode the signals in the brain's environment through biomarkers in the blood.

microvesicles are a window into the brain that allows us to listen to the language of the brain cells

In the study, researchers analysed blood samples from 39 patients with acute stroke and an equally sized control group and studied microvesicles from brain pericytes, cells wrapping small blood vessels in the brain. Pericytes are cells that respond quickly to the sudden lack of oxygen that occurs during a stroke and send important signals on to other cells.

Microvesicles are small vesicles released by cells that can be traced back to the cell of origin using specific markers. They contain important signalling molecules used to coordinate the brain's activities and other bodily functions, information that is crucial for the bodies response to stroke. Microvesicles can travel long distances, can be extracted from the blood and their content can be analysed.

"The content of microvesicles helps us understand brain cell signals at different time points after a stroke. They can be used as biomarkers and thus provide information about the communication between cells. Simply put, microvesicles are a window into the brain that allows us to listen to the language of the brain cells via the blood," says Gesine Paul-Visse, adjunct professor at Lund University and Senior Consultant at Skåne University Hospital who led the study.

The study was conducted in close collaboration with Arne G Lindgren, professor at Lund University, Senior consultant at Skåne University Hospital, and head of the Lund Stroke Register.

"We have about 650 kilometres of blood vessels in the brain, and pericytes act as gate keeper, responsible for the exchange between the blood and what is allowed to enter the brain. They play an important role in protecting and stabilizing the blood-brain barrier, which functions as a firewall around the brain. Pericytes are also the cells that initiate the formation of new blood vessels after a stroke," explains Andreas Enström, co-author of the study that is part of his PhD thesis.

During a stroke, pericytes in the small blood vessels are affected, contributing to the breakdown of the blood-brain barrier. The researchers show that the amount of microvesicles released from pericytes increases in the blood of patients who have had an ischemic stroke. Even though at 0-6 hours after the stroke, stroke patients and the control group still had approximately the same amount of microvesicles in the blood, at 12-24 hours after the stroke, the amount of microvesicles significantly increased in those affected by the stroke compared to the control group. This increase remained at the same levels in the measurement taken 2-6 days after the stroke. Interestingly, analyses of the microvesicles' content also showed a change over time.

"After a while, pericytes not only send signals that affect inflammation but also signals that are needed for the rebuilding of blood vessels. Identifying potentially harmful signals mediated by pericytes and blocking their release during a stroke is an opportunity to develop new treatments in the future that could slow down the pathological progression during a stroke," says Andreas Enström.

The researchers now plan to expand their studies to include other cell types in the brain and investigate their communication during a stroke. Their goal is to identify potential therapeutic targets that can be used to reduce damage and improve recovery after a stroke.

"This opens up new opportunities for researchers to study stroke, and we hope that understanding what happens in the brain at the molecular level will eventually improve the prognosis for those affected. We now want to investigate the communication from other brain cell types during a stroke in a larger material," says Gesine Paul-Visse, corresponding author of the study.

Facts

Microvesicles are small vesicles released from cells that can travel long distances, transporting signals between different cells, and thus playing a vital role in cellular communication. The signals in microvesicles can affect many physiological processes, including the immune system, inflammatory reactions, and the formation of new blood vessels.

Publication

Pericyte Microvesicles as Plasma Biomarkers Reflecting Brain Microvascular Signaling in Patients With Acute Ischemic Stroke”
Stroke, februari 2024
Abderghaim Gaceb, Linnea Roupé, Andreas Enström, Wejdan Almasoudi, Robert Carlsson, Arne G. Lindgren och Gesine Paul-Visse.

This work was supported by the Swedish Research Council, the Swedish Brain Foundation, the Crafoord Foundation, the Anérs Foundation, and the Olle Engkvist Foundation, The Swedish Government (under the Avtal om Läkarutbildning och Medicinsk Forskning, ALF), The Swedish Heart and Lung Foundation, The Swedish Stroke Association, Region Skåne, Lund University, Skåne University Hospital, and the Freemasons Lodge of Instruction Eos in Lund.

Contact

Gesine Paul-Visse, PI, Adjunct professor, Associate Professor at Lund University, Consultant in Neurology, MD, Skåne University Hospital
Profile in Lund University Research Portal

Andreas Enström, PhD, researcher in the research group Translational Neurology, Lund Universityl
Profile in Lund University Research Portal