In the US alone, more than 750,000 people had a stroke in 2017, more than 1.7 million reported a traumatic brain injury, and more than 9 million suffered from migraines with aura. While all three of these neurological conditions have vastly different causes and possible outcomes they all have a common phenomenon occurring within the brain. A wave that slowly propagates through grey matter, hitting neurons with a large burst of energy, opening them up to a flood of ions and silencing them for an extended period of time. These waves are known as spreading depolarizations (SD). Within well-nourished tissue, neurons recover from SD. However, in vulnerable tissues, SD events can cause step-wise increases in injury. There are currently no approved treatments that specifically target SD. Understanding the progression of SD may lead to a better plan for targeting these waves in the future.
Using preparations from mice we have investigated factors which “prime” SD to propagate more quickly through brain. We found that firing of brain cells in advance of an SD wave can accelerate SDs. Additionally, accumulation of potassium ions can prime tissues to be more susceptible to an SD traveling through a region of brain, and that this can be sufficient to launch an SD event from a remote location following a relatively benign stimulus. Our results also demonstrate interactions of multiple SDs. These results increase understanding of the factors responsible for propagating SDs, which may lead to development of new approaches to interrupt these damaging events.
Spreading depolarization, Stroke, Neuron, Brain injury, Hippocampus, Trisynaptic circuit
Level of Degree
First Committee Member (Chair)
C. William Shuttleworth
Second Committee Member
Third Committee Member
Selters, Linday. "Factors that Determine Spreading Depolarization Propagation in Brain Slices." (2018). http://digitalrepository.unm.edu/bme_etds/18