New research reveals how nerve cells protect themselves against stroke damage
18 August 2011
According to the Stroke Association, stroke is the third most common cause of death in the UK. It causes disruption to the blood supply to the brain, depriving nerve cells of oxygen and nutrients, which leads to the death of nerve cells and the consequent loss of the brain's cognitive functions, such as speech and movement; however, not all nerve cells are equally susceptible to stroke-induced damage.
Dr Jack Mellor from the University of Bristol, funded by the Medical Research Council and the Wellcome Trust, led a study examining two types of nerve cell in the hippocampus (a region of the brain linked to memory and navigation). One of these cell types, the CA1 cell, is highly susceptible to damage after stroke, whereas the other, the CA3 cell, is much more resistant - despite the many similarities between the two cell types.
"We hope that if we can understand why some nerve cells are resistant to stroke damage, we may be able to develop strategies to protect those cells that are sensitive," explained Dr Mellor.
The researchers found that the CA3 cells possess a mechanism for reducing their susceptibility during, and immediately after, a laboratory-based model for stroke. This mechanism involves making the CA3 cells less sensitive to the neurotransmitter glutamate by removing glutamate receptor proteins from the surface of these cells. Glutamate is released in large quantities during stroke.
The removal of these receptors is triggered by adenosine A3 receptors, which are activated by very high levels of adenosine, a neurotransmitter found at elevated levels during stroke. CA1 cells that are susceptible to stroke damage do not have adenosine A3 receptors and therefore do not possess the mechanism to remove surface glutamate receptors in response to the stroke model.
Dr Mellor added: "Historically, stroke has been very difficult to treat because of its unpredictability and the need to administer drugs within minutes of the onset of a stroke. These problems will not be overcome by our research but our findings do reveal a natural protection mechanism in some nerve cells, which may be useful in developing treatments to protect other nerve cell types."
Image: Hippocampal neurons labelled with an antibody against the GluR1 subtype of glutamate receptors. Credit: A J Irving, Wellcome Images.
Reference
Dennis SH et al. Oxygen/glucose deprivation induces a reduction in synaptic AMPA receptors on hippocampal CA3 neurons mediated by mGluR1 and adenosine A3 receptors. J Neurosci 2011 [epub ahead of print].
