Acute brain injuries have devastating consequences for patients and their families. For example, traumatic brain injury (TBI) is one of the leading causes of death, notably in young males. Brain injury after trauma is categorized into two pathological mechanisms. The early brain injury is the direct impact on the brain tissue, and secondary injury involves multiple, deleterious biological interactions that follow, notably through oxidative stress and inflammatory injury.
Although most iron is found bound to iron-binding proteins, this balance shifts after trauma toward an increase in the chelatable iron pool. Iron is postulated to contribute to secondary injury as it triggers the Fenton reaction leading to a surge in free radicals and subsequent inflammation. The Doré Lab has been postulating that this shift is triggered by the lysis of red blood cells which then release ~250M molecule of hemoglobins. Each hemoglobin then releases four heme molecules and at the core, has iron. To prevent iron accumulation, iron chelators are being tested. The Doré Lab has discovered that the iron chelator N,N’-Di(2-hydroxybenzyl)ethylenediamine-N,N’-diacetic acid monohydrochloride (HBED) could be a neuroprotective agent after TBI. HBED is an iron chelator and hydroxyl radical inhibitor containing unique characteristics such as the ability to cross not only the intact blood-brain barrier (BBB) but also into brain cells and mitochondrial membranes. Additionally, it possesses a higher affinity and selectivity toward iron compared to other iron chelators. Part one of my project will be to evaluate the effect of iron chelator in TBI, focusing on white matter loss. In the second part of my project, I will investigate the iron chelator’s role in ischemic stroke.