Faculty of Biological Sciences

Research Bulletin

Stroke damage mechanism identified

30th January 2015

FBS Researchers have discovered a mechanism linked to the brain damage often suffered by stroke victims—and are now searching for drugs to block it.

Stroke damage mechanism identifiedtitle=

FBS Researchers have discovered a mechanism linked to the brain damage often suffered by stroke victims—and are now searching for drugs to block it.

Strokes happen when the blood supply to part of the brain is cut off but much of the harm to survivors’ memory and other cognitive function is often actually caused by “oxidative stress” in the hours and days after the blood supply resumes.

A team from the University of Leeds and Zhejiang University in China studied this second phase of damage in laboratory mice and found a mechanism in neurons that, if removed, reduced the damage to brain function.

Co-author Dr Lin-Hua Jiang, of the University of Leeds’ School of Biomedical Sciences, said: “Until now, much of the drug research has been focussing on the direct damage caused by the loss of blood flow, but this phase can be hard to target. The patient may not even be in the ambulance when it is happening. We have found a mechanism that is linked to the next phase of damage that will often be underway after patients have been admitted to hospital.”

The study, published in the journal Cell Death and Disease andsupported by a strategic partnership between the University of Leeds and Zhejiang University, looked at the damage caused by the excessive production of chemicals called “reactive oxygen species” in brain tissues immediately after blood supply is re-established. In a healthy brain, there are very low levels of reactive oxygen species, but the quantity dramatically increases after a stroke to levels that are harmful to neurons.

Dr Jiang said: “We identified an ‘ion channel’ in the membranes of neurons, called TRPM2, which is switched on in the presence of the reactive oxygen species. Basically, an ion channel is a door in the membrane of a cell that allows it to communicate with the outside world— TRPM2 opens when the harmful levels of reactive oxygen species are present and we found that removing it significantly reduced neuronal cell damage.”

The researchers compared the effects of strokes on mice with TRPM2 with a transgenic strain without it.

In the mice in which the TRPM2 channel does not function, the reactive oxygen species are still produced but the neurons are very much protected. The neuronal death is significantly reduced. More importantly, we observed a significant difference in brain function, with the protected mice demonstrating significantly superior memory in lab tests.

 “This study has pinpointed a very promising drug target. We are now screening a large chemical library to find ways of effectively inhibiting this channel. Our ongoing research using animal models is testing whether blockage of this channel can offer protection again brain damage and cognitive dysfunction in stroke patients” Dr Jiang said.

The research was funded by the Royal Society, Alzheimer’s Research UK, the Natural Science Foundation of China and the National Basic Research Program of China. 

View full article


Recent Grants

Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521

Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015

Bill Kunin, EU (Jan 2015), £157,490

John Colyer, Leeds Teaching Hospitals Charitable Fund (Jan 2015), £40,000

Chris Hassall, Royal Society (Dec 2014), £14,500

Ryan Seipke, Royal Society (Nov 2014), £13,700

Alan Berry, Wellcome Trust (Oct 2014), £749,865

Ian Hope, Marie-Anne Shaw, BBSRC (Oct 2014), £396,565

Alison Ashcroft, Peter Stckley, Sheena Radford, Nic Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Oct 2014), £340,937

Les Firbank, Joe Holden, BBSRC (Oct 2014), £210,302

Darren Tomlinson and colleagues in Chemistry and Pathology, anatomy and Tumour Biology, Dr Hadwen Trusy (Oct 2014), £194,475

Paul Knox, EU (Oct 2014), £167,229

Martin Stacey and colleagues in Medicine & Health, Pfizer (Oct 2014), £90,453

Darren Tomlinson and colleagues in Experimental Oncology, YCR (Oct 2014), £69,480

Andrew Macdonald, Jamel Mankouri, Kidney Research Fund UK (Oct 2014), £58,878

Mike McPherson and colleagues in Dentistry and Engineering, Wellcome Trust (Oct 2014), £58,437

Dave Westhead and colleagues in Experimental Haemotology, Leukaemia & Lymphoma Research (Sep 2014), £281,424

Emmanuel Paci and colleagues in Chemistry, BBSRC (Sep 2014), £636,759

Andrew Peel, BBSRC (Sep 2014), £371,598

Lars Jeuken, Stephen Evans, BBSRC (Sep 2014), £333,684

Lars Jeuken, BBSRC (Sep 2014), £313,463

Michelle Peckham, Mark Harris, Rao Sivaprasadarao, Eileen Ingham, Nic Stonehouse, Nikita Gamper, Wellcome Trust (Sep 2014), £192,763

Neil Ranson, BBSRC (Aug 2014), £355,253

Stuart Egginton, BHF (Aug 2014), £271,094

Darren Tomlinson, Mike McPherson, Technology Strategy Board (Aug 2014), £98,665

Peter Henderson, Leverhulme Trust (Aug 2014), £15,222

Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880

Peter Stockley, Neil Ranson, BBSRC (Jul 2014), £455,787

Sheena Radford, Univesity of Michigan (Jul 2014), £138,452

Ryan Seipke, British Society Antimicrobial Chemistry (Jun 2014), £11,960

John Trinick, BHF (Jun 2014), £222,614

Chris West, Leverhulme Trust (Jun 2014), £181,241

Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174

Christine Foyer, Royal Society (May 2014), £24,000

David Brockwell, Sheena Radford, Medimmune Ltd (Apr 2014), £337,661

Peter Stockley, Wellcome Trust (Apr 2014), £251,019

Mike McPherson, Wellcome Trust (Apr 2014), £146,596

Andrew Macdonald, Kidney Research Fund UK (Apr 2014), £127,237

Elwyn Isaac, DEFRA (Apr 2014), £126,512

Mike McPherson (and colleagues in School of Design), Technology Strategy Board (Apr 2014), £114,350

Paul Millner, Peter Stockley, Darren Tomlinson, YCR (Apr 2014), £95,874

Carrie Ferguson, Karen Birch, Shaunna Burke, Heart Research UK (Apr 2014), £60,140

Tim Benton, Technology Strategy Board (Apr 2014), £24,969

Bill Kunin, Technology Strategy Board (Apr 2014), £21,244

Dave Westhead, MRC (Apr 2014), £18,304

Brendan Davies, BBSRC (Mar 2014), £451,829

Jim Deuchars, MRC (Mar 2014), £300,000

Urwin, Howard Atkinson, British Potato Council (Mar 2014), £69,953

Adam Kupinski, Children with Cancer (Mar 2014), £50,000

Anastasia Zhuravleva, Royal Society (Mar 2014), £14,973

Urwin, Howard Atkinson, Agriculture & Horticulture Develpmnt Brd (Mar 2014), £13,990

Alison Baker, Steve Baldwin, BBSRC (Feb 2014), £403,439

Sarah Zylinski, BBSRC (Feb 2014), £355,869

Dave Lewis, Nigel Hooper, Tony Turner, Hugh Pearson, James Duce, Alzheimer's Society (Feb 2014), £29,871

Recent News

Impact Stories

Research by Dr Keith Hamer on the foraging and breeding ecology has had impact in the understanding of interactions between seabirds and fisheries.
more

Professor Eileen Ingham has led research over many years to develop improved approaches to aid healing and repair of soft tissues.
more

Dr Simon Goodman has investigated the disease risks to the native Galapagos fauna.
more

Professor Paul Milner has led a team of scientists on a project to develop antibody-based biosensor technologies.
more

All impact stories