Stroke damage mechanism identified
News Nov 27, 2014
Researchers have discovered a mechanism linked to the brain damage often suffered by stroke victims -- and are now searching for drugs to block it.
While strokes cut off blood supply to parts of the brain, 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 and supported by a strategic partnership between the University of Leeds and Zhejiang University, looked at the damage caused by the excessive production 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," Dr Jiang said.
"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.
Note: Material may have been edited for length and content. For further information, please contact the cited source.
M. Ye, W. Yang, J.F. Ainscough, X.-P. Hu, X. Li, A. Sedo, X.-H. Zhang, X. Zhang, Z. Chen, X.-M. Li, D.J. Beech, A. Sivaprasadarao, J.-H. Luo, L.-H. Jiang. TRPM2 channel deficiency prevents delayed cytosolic Zn2 accumulation and CA1 pyramidal neuronal death after transient global ischemia. Cell Death and Disease, Published Online November 27 2014. doi: 10.1038/CDDIS.2014.494
A recent retrospective study evaluating continuous electroencephalography (cEEG) of children in intensive care units (ICUs) found a higher than anticipated number of seizures. The work also identified several conditions closely associated with the seizures, and suggests that cEEG monitoring may be a valuable tool for helping to identify and treat neurological problems in patients who are 14 months old or younger.
Pain is a negative feeling that we want to get rid of as soon as possible. In order to protect our bodies, we react for example by withdrawing the hand. This action is usually understood as the consequence of the perception of pain. A team from the Technical University of Munich (TUM) has now shown that perception, the impulse to act and provision of energy to do so take place in the brain simultaneously and not, as was expected, one after the other.