Stroke: Domino Effect

We all understand that a stroke occurs when a blood vessel in the brain becomes blocked by a clot or bursts, eventually leading to decreased O2 and glucose supply to that particular brain tissue. As a result, this tissue will either become damaged or die. However, according to Lauralee Sherwood, there is a lot more to the causes of brain damage than what’s been told. She calls it “A Deadly Domino Effect.”

Some recent findings suggest that neurotoxic effects create a broader area for cell death. In other words, not only are the initial blood-deprived cells dieing by necrosis (accidental cell death), but their neighboring cells are also subject to apoptosis (intentional cell death). There is a cascade of events that begins with the initial O2 deprived cells which releases enormous amounts of glutamate, a common excitatory neurotransmitter. Normally, it is dispersed in small amounts, enough for chemical communication between brain cells. The excitatory glutamate overproduced and released by the damaged brain cells attaches to and overexcites bordering neurons. Glutamate specifically likes to bind with NMDA receptors, which function as Ca2+ channels. The toxic activation of these receptor-channels causes the channels to remain open longer which allows even more Ca2+ to flood into the affected neighboring neurons. As a result, the elevated levels of intracellular Ca2+ activate the apoptosis of these cells.

But wait, there’s more. The Ca2+ apoptotic signal is speculated as spreading from dying cells to adjoining healthy cells. This job is accomplished through gap junctions, cell-to-cell conduits that permit the diffusion of Ca2+ and other small ions between cells. Overall, what does this tell us about a stroke? The majority of neurons that die following a stroke are originally unharmed cells that commit suicide in response to the chain of reactions unleashed by the toxic release of glutamate from the initial site of O2 deprivation.


Sherwood, Lauralle. Human Physiology 6th Ed. United States: Thompson Brooks/Cole, 2007.