A thin layer of cells lines our arteries and veins. These cells are held tightly together by specialized proteins that function like strong ropes (red) and others that act like cement (blue). Image credit: Christopher Carman, Roberta Martinelli (CC BY-NC 2.0)
A stroke can cause long-lasting physical and mental disabilities in patients including loss of mobility, speech defects and confusion. Most strokes happen when the blood supply to part of the brain is cut off due to blood clots or clumps of fat blocking blood vessels called arteries. To prevent a blocked blood vessel causing a stroke, the network of blood vessels in the brain contains alternative routes to each area. The arteries in these alternative routes can widen to allow more blood to flow through them and avoid the blockage.
When the blood supply to part of the brain is cut off, the level of oxygen in that area decreases. This causes highly reactive molecules known collectively as free radicals to be produced, which can bind to other molecules in cells and stop them from working properly. A protein called TRPA1 is found in the cells that form the inner lining of blood vessels. When it is active, TRPA1 forms a channel that allows signals known as calcium ions to enter the cell, which ultimately leads to arteries in the brain becoming wider. A free radical known as 4-HNE binds to TRPA1, but it is not clear if this enables the channel to directly sense the levels of oxygen in the brain.
Pires and Earley studied TRPA1 channels in brain arteries from mice. The experiments found that decreasing the levels of oxygen in the arteries caused 4-HNE to accumulate and activate TRPA1, resulting in the blood vessels becoming wider. Chemicals that inhibit the production of free radicals blocked the activity of the TRPA1 channels. Mice that lacked TRPA1 were more likely to sustain damage to the brain during strokes than normal mice. Furthermore, injecting normal mice experiencing a stroke with a drug that activates TRPA1 reduced the amount of damage to the brain.
The findings of Pires and Earley suggest that TRPA1 plays an important role in protecting the brain during strokes and other conditions that reduce the brain’s blood supply. Future studies will assess whether drugs that activate TRPA1 have the potential to help reduce long-term disabilities in human patients who have a stroke.
