New therapies for stroke patients may soon be possible, thanks to a discovery made by a team of University of British Columbia neuroscience researchers who have found a new stroke death channel -- the conduit through which key chemicals are lost from brain cells during stroke, causing the cell death that disables stroke victims.
The findings were published recently in Science and will be the subject of an editorial in next month’s issue of Nature Reviews Neuroscience.
“We’ve known for 40 years about chemicals flowing out of cells after stroke, but nobody knew the exact process -- so we went looking for the death channel. And we found it,” says Roger Thompson, a UBC Psychiatry post-doctoral Fellow who made the discovery, along with graduate student Ning Zhou and Psychiatry Prof. Brian MacVicar, all members of the Brain Research Centre at UBC Hospital and of Vancouver Coastal Health Research Institute.
The researchers found, in animal models, that brain cell membranes were disrupted at the site of gap junction hemichannels. Gap junctions are connections that allow molecules and ions to flow between cells. Junctions are composed of two hemichannels that bridge the intercellular space.
Until now, scientists believed the disruption to occur at the site of glutamate channels. Glutamate is one of the brain’s most abundant chemical messengers. However, therapeutic strategies targeted at glutamate channels failed to prevent brain cell death.
“Our discovery was unexpected -- we’re now going to change channels and pursue a completely different research direction,” says MacVicar, Canada Research Chair in Neuroscience. “This finding offers new possibilities for stroke therapies and reinforces the value of investing in basic science research.”
When stroke occurs, hemichannels can form outside the junction and leak chemicals. The process drastically disrupts levels of critical brain cell ingredients such as calcium and potassium, and is associated with rapid cell death.
Every year, 50,000 Canadians suffer a stroke. Another 300,000 people are living with the consequences of stroke, which is the leading cause of adult disability in Canada.
The next step in the investigation will be to determine the cause of the hemichannel malfunction. Scientists can then develop a compound to block brain cell hemichannels from opening, says MacVicar. Therapies for stroke patients may be available within five to 10 years, he adds.
The Brain Research Centre comprises more than 150 investigators with multidisciplinary expertise in neuroscience research ranging from the test tube, to the bedside, to industrial spin-offs. The centre is a partnership of UBC and Vancouver Coastal Health Research Institute, the research body of the health authority.
Support for the study has been provided by:
* The Canadian Stroke Network, one of Canada’s Networks of Centres of Excellence, that includes more than 100 of Canada’s leading scientists and clinicians from 24 universities who work collaboratively on various aspects of stroke.
* The Heart and Stroke Foundation, a leading funder of heart and stroke research in Canada, that aims to improve the health of Canadians by preventing and reducing disability and death from heart disease and stroke through research, health promotion and advocacy.
* CIHR, the Government of Canada’s agency for health research. Composed of 13 Institutes, CIHR provides leadership and support to close to 10,000 health researchers and trainees across Canada.
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