Stroke of luck

“This really opens up a new area for stroke research.”

– Dr Ruth Slack, professor at the Faculty of Medicine

By Chonglu Huang

Scientists from the Faculty of Medicine at the University of Ottawa Brain and Mind Research Institute (uOBMRI) have made a significant breakthrough in stroke research that may lead to greater clinical outcomes for patients.

In the event of a stroke, blocked blood vessels and hemorrhaging inhibit the flow of oxygen to the brain, causing immediate cell death in the primary stroke area and threatening further cell death in the surrounding area over a period of several days.

“This is why someone having a stroke may be okay at the time of the episode, but then three or four days later, they lose their memory or experience loss of bodily functions,” says Dr. Ruth Slack, a professor in the Faculty of Medicine, Department of Cellular and Molecular Medicine.

With this in mind, Dr. Mireille Khacho, a postdoctoral fellow working with Dr. Slack, focused her research on preserving the function of cells surrounding the stroke core so that they can continue to produce energy and perform activities essential to human life.

Using an in vitro model where neurons are placed in a low-oxygen setting, mimicking what is seen in the brain during stroke, Khacho made an important discovery — that acidosis, a physiological consequence of oxygen deprivation, can have protective effects on cells, allowing them to survive and even thrive in low-oxygen environments.

This clinical experiment demonstrates that certain levels of acidosis allow mitochondria — the energy-making furnaces of the cells — to change shape to become more efficient, require less oxygen to function and essentially become more resilient in an otherwise detrimental setting.

“People used to think that acidosis was purely a toxic by-product of oxygen deprivation that caused unavoidable cell deaths,” explains Khacho. “But starting 10 years ago, scientists began to realize that depending on the level of acidosis, it can be protective and help cells survive in horrible stress conditions.”

Published on April 1, 2014 in Nature Communications, a high-impact natural sciences journal, the implications of these findings are highly significant for curbing stroke damage and increasing the chance for patient recovery.

“If we have a way to go in mechanistically — perhaps with a drug — to reconfigure these mitochondria to make them stronger and healthier, then you can prevent neurodegeneration after stroke,” says Khacho.

“Until now, nobody has been able to show that mitochondria can be reconfigured at times when they would normally self-destruct, and this really opens up a new area for stroke research,” adds Dr. Slack.

The research was based at the Ruth Slack Laboratory at the University of Ottawa Brain and Mind Research Institute and supported by the Heart and Stroke Foundation of Ontario, Brain Canada/Krembil Foundation and the HSF Canadian Partnership for Stroke Recovery.

Main photo:
Professor Ruth Slack (at left) and postdoctoral fellow Mireille Khacho.

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