Grant: Operating Grant

It is well established in people and animals that both seizures and episodes of low tissue oxygen levels result in a number of deleterious effects to the brain that lead to disruptions in cognitive functioning and behaviour. Given the similarities between these two types of devastating conditions, I reasoned that each seizure may lead to a cascade of events that result in low brain oxygen levels. We implanted a small device that provides accurate and continuous measurements of oxygen levels in a local area of brain tissue in awake freely moving rats and then induced a brief (<1 minute) seizure. We discovered a severe and long-lasting episode of extremely low oxygen that begins minutes after a seizure is terminated and lasts about an hour. We have also measured blood flow and found that the seizure-induced low oxygen episodes are related to reduced blood flow to the brain region involved in the seizure. My data suggest the following General Hypothesis: Seizures result in very low brain tissue oxygen levels (hypoxia) which is mediated by local blood flow mechanisms (ischemia) that, in turn, results in transient behavioural impairment, a series of injurious outcomes to brain and alterations in learning. Understanding that seizures lead to reduced blood flow and low oxygen levels is critically important, because a key factor by which seizures could result in deleterious effects to the brain is through the resulting low oxygen levels, and not just the immediate seizure itself. Moreover understanding the mechanisms of seizure-induced low oxygen levels is critical for determining and implementing therapies that treat this previously unrecognized source of injury that long outlasts a seizure event. Our work indicates that in addition to preventing seizures, people with seizure disorders, particularly those who have recurrent spontaneous seizures (epilepsy), may benefit from accessing therapies that prevent the reduced blood flow and resulting low oxygen levels.