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A team of international collaborators including DPAG's Dr Mootaz Salman has been researching a promising new therapeutic for the treatment of strokes and other brain injuries.

Effect of TFP on brain metabolic markers after stroke. Representative images of FTIR spectroscopic imaging at 24 h post-stroke in non-treated stroke and sham animals, and animals treated with TFP at 30 minute pre- stroke or 1 h post-stroke.
FTIR spectroscopic imaging shows the effect of trifluoperazine (TFP) on brain metabolic markers after stroke

Researchers from the University of Saskatchewan, Columbia University and the University of Oxford have used synchrotron imaging, combined with traditional techniques, to assess the effects of an FDA-approved antipsychotic medication, known as trifluoperazine (TFP), during the acute phase post stroke.

With the help of the Canadian Light Source (CLS) at the University of Saskatchewan (USask) and the Stanford Synchrotron Radiation Light Source (SSRL), the team was able to measure subtle changes in the biochemistry of brain tissue – measurements that are only possible with the use of a synchrotron.

“The synchrotron at the CLS provides us with a tool that allowed us to map unprecedented levels of brain detail,” said co-first author and corresponding author Dr Mootaz Salman, DPAG Research Scientist at the Oxford Parkinson's Disease Centre and Junior Research Fellow at Wolfson College.

Already approved for human use in the treatment of schizophrenia, the team believes that TFP has the potential to stop the swelling in the brain that occurs after a stroke or other cerebral injury.

“According to the World Health Organization, around 60 million people sustained a traumatic brain or spinal cord injury and a further 15 million people suffered from a stroke in 2020,” said Dr Salman. “Edema, which is swelling due to water or other body fluid accumulation, is the hallmark of stroke and plays a major role in stroke-associated morbidity and mortality.”

USask professor and Saskatchewan Clinical Stroke Research Chair Dr Michael Kelly, says that the CLS played an important role in understanding how TFP could be used for stroke patients. “Synchroton imaging has facilitated research on effects of stroke on brain energy metabolism and elemental distribution, which has given us new insights into stroke treatment.”

Dr Salman and Dr Kelly’s team has demonstrated that a dose of TFP reduces edema in a mouse model of stroke—a breakthrough that could lead to the development of new treatment options for stroke patients.

TFP acts on doughnut-shaped water channel proteins, called aquaporins, in brain cells. During a stroke, the brain’s blood supply is restricted, which prevents cells from receiving enough oxygen. These oxygen-starved cells are unable to do their usual job of maintaining a balance of fluid, nutrients and electrolytes within the brain, leading to severe swelling.

“Water rushes from the outside through these doughnut-shaped proteins, into the cells that then swell,” Dr Salman said. “The build-up of pressure damages the fragile brain tissue, disturbing the flow of electrical signals from the brain to the body.”

TFP stops this from happening by preventing a signal that would normally cause more aquaporin channels to rise to the surface of brain cells. Other treatments — which often include invasive surgeries — are techniques used to manage symptoms and minimize damage that has already occurred.

TFP is already a licensed medicine, Dr Salman says it could be rapidly repurposed for use in new therapeutic protocols for stroke during the early acute phase.

“Our novel approach offers new hope for patients with central nervous system injuries and strokes and has a huge therapeutic potential. These findings suggest it could be a good candidate for early phase of human clinical application at a low treatment cost in the near future,” Dr Salman said.

Story by Erin Matthews on the Canadian Light Source website.

The full paper "The effects of trifluoperazine on brain edema, aquaporin-4 expression and metabolic markers during the acute phase of stroke using photothrombotic mouse model" is available to read in BBA-Biomembranes.

This story has been covered by CTV News in "Huge therapeutic potential': University of Sask. researchers make progress on stroke treatment" and a video interview can be watched on the CTV News Regina website. A podcast is also available hosted by Gormley on Demand and a news article on CBC News: "Potential treatment for stroke, brain injury studied with help from Saskatoon's synchrotron

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