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Cancer drug shows potential for improving stroke recovery

A cancer drug has been shown to significantly improve stroke recovery in diabetic mice by reducing the leakiness of blood vessels in the brain – a discovery that could eventually lead to better recovery rates for diabetic patients after stroke, according to a Canadian study published today in the journal Neuroscience.

“A big challenge in treating stroke is understanding how other health conditions affect recovery. Many diseases increase the chances of having a stroke, and limit recovery. Diabetes is one of these diseases, affecting millions in Canada,” says lead author Dr. Craig Brown, an Associate Professor at the University of Victoria.

“Much like a five-card poker hand, the unique collection of health concerns a patient holds in their hand likely dictates how they should be treated.”

The reasons behind the poorer prognosis for recovery in people living with diabetes, let alone strategies for addressing it, are unknown. However, Dr. Brown’s lab is providing new answers to these questions.

“What we have found is that diabetic mice have leakier blood vessels in the brain after stroke than mice without diabetes. These leakier vessels lead to greater movement of proteins and other damaging elements of blood plasma into the brain, a process that is normally regulated in a strict manner to protect brain health,” Dr. Brown says.

The three-year study traces the cause of leaky vessels to excessive vascular endothelial growth factor (VEGF) signaling, which regulates the growth and permeability of blood vessels.

Fortunately, several clinically tested VEGF inhibitors have been developed over the last few decades to block cancerous tumors from growing new blood vessels and spreading. Dr. Brown’s lab used one of these cancer drugs, as well as a genetic knockdown approach to determine if they could reduce blood vessel leakage and the damaging effects of stroke.

As it turned out, the treatment not only helped reduce the leakiness of blood vessels, but it also prevented the loss of neural connections and improved the recovery of sensory-motor function in diabetic mice, which could lead to improved treatment for diabetic patients after stroke.

“Quite surprisingly, however, the same treatment had no benefits in non-diabetic mice, suggesting that when it comes to betting on a stroke treatment, you really have to know what cards you are holding,” Dr. Brown says.

Dr. Dale Corbett, Scientific Director and CEO of the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, says the study published by Brown and colleagues in the April 1 issue of the Journal of Neuroscience is noteworthy for two reasons.

“First, they show in mice with an existing diabetic condition that a drug (SU5416 or Semaxanib), commonly used to block a vascular endothelial growth factor (VEGF) signalling pathway in the treatment of cancer, was able to reduce post-stroke vascular damage (i.e. leaky vessels) as well. This in turn helped attenuate post-stroke structural damage of cortical neurons and improved behavioural outcome,” Dr. Corbett says.

“The second intriguing aspect of their study is that this drug treatment was only beneficial in diabetic mice; it did not help non-diabetic stroke mice. This important observation reinforces the notion that treatment for stroke, like so many other diseases, must be individually tailored to address co-existing disease states. In other words, one size does not fit all!”

For further information, see the study in the April 1st edition of the Journal of Neuroscience.

Dr. Brown’s neurobiology lab employs in vivo microscopic imaging technologies such as two-photon microscopy and functional imaging of neuronal and hemodynamic activity that allow the visualization of neuronal structures deep within the living brain or the processing of sensory information in real-time. A central goal of Dr. Brown’s research program is to use these experimental approaches to characterize the neurobiological mechanisms that allow the cerebral cortex to develop normally and change throughout life in response to new experiences (eg. learning, drug exposure) or pathology such as stroke or diabetes.

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