Discovery of a protein that could promote recovery after a stroke

Discovery of a protein that could promote recovery after a stroke
Discovery of a protein that could promote recovery after a stroke

Researchers at Laval University have shed light on the key role of a brain protein in the repair of damaged tissues following a stroke. Their breakthrough, which has just been the subject of a publication in the journal Cellular and Molecular Life Sciencessuggests the possibility of using this protein to develop a new treatment for people suffering from stroke.

The protein in question, PDGF-D, was discovered around ten years ago. “In mice, this protein is produced transiently in the brain after a stroke by cells that line the inside of blood vessels, the endothelial cells. The peak production of this protein occurs three days after the stroke. PDGF-D is also produced in humans, but its function in the brain was not yet known,” explains the head of the study, Ayman ElAli, professor at the Faculty of Medicine at Laval University and researcher. at the Research Center of the CHU de Québec-Université Laval.

The only known receptors for PDGF-D are on cells, called pericytes, which are located at the interface between nerve cells and blood vessels in the brain. This is what prompted researchers to study the link between pericytes and PDGF-D. “Pericytes are specialized cells which play an essential role in the regulation of cerebral blood flow and which serve as an interface for exchanges between blood and nerve cells,” explains Professor ElAli. We know that a stroke can cause pericytes to die or disrupt their functioning.”

To understand how PDGF-D affects pericytes, the researchers first induced underexpression of this protein in mice used as a study model for stroke. “In the days following stroke, we found that the decrease in PDGF-D was associated with higher neuronal mortality, reduced microvessel density, and occlusion of new vessels that were forming. in their brains,” points out Professor ElAli.

The next experiment, which consisted of administering the PDGF-D protein into the nasal cavity of mice after a stroke, delivered diametrically opposite results. “We observed an increase in neuronal survival and better neuronal recovery. Additionally, the density of cerebral blood vessels increased, which led to improved blood flow in the brain.”

Experiments carried out in vitro with endothelial cells and pericytes collected from humans led to these similar conclusions.

“Our results suggest that the PDGF-D protein is a call for help that blood vessels send to pericytes after a stroke,” explains Professor ElAli. This SOS stimulates pericytes which respond by ensuring the maintenance of the structure and functions of blood vessels as well as the production of new blood vessels. Through this, oxygen and nutrients essential for the survival of neurons and the repair of tissues damaged by stroke can be delivered to the brain.

“ It is a molecule that exists naturally in the body, we know how to synthesize it in the laboratory and it is possible to administer it non-invasively via the nasal route. »

— Ayman ElALi

In light of these results, the idea of ​​administering the PDGF-D protein to people who have just suffered a stroke springs to mind. “It is a molecule that exists naturally in the body, we know how to synthesize it in the laboratory and it is possible to administer it non-invasively via the nasal route. Technically, its use to mitigate the damage caused by a stroke and to promote tissue repair is possible. It remains to be demonstrated in humans,” concludes Professor ElAli.

The other authors of the study published in Cellular and Molecular Life Sciences are Maxime Bernard, Romain Menet and Sarah Lecordier.

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