Presenter
Tiffany Kung, Neuroscience and Mental Health Institute, University of Alberta
Abstract
Intracerebral hemorrhage (ICH) is a devastating stroke with various damage mechanisms, including ionic dyshomeostasis (ion concentration imbalances) and edema (brain swelling). Ion channels expressed after stroke, such as Sur1-Trpm4 which brings sodium ions and water into cells, are hypothesized to contribute to this. In severe ICH, edema can lead to cell death and high mortality. One treatment targeting ion channels is glibenclamide, which blocks Sur1-Trpm4 and may reduce edema and ionic dyshomeostasis in pre-clinical models of severe ischemic stroke. Despite the upregulation of Sur1-Trpm4 in both stroke subtypes, this drug has never been tested for treating severe ICH. We hypothesize that glibenclamide will lessen edema and ionic dyshomeostasis to improve behavioural recovery. In the first experiment (n=7-8), bleed volume and behaviour were assessed 24 hours after ICH. As larger bleed volumes correlate to worse outcome, if glibenclamide worsened bleeding, it would be unlikely to confer benefit. As expected, the drug did not affect bleeding (p=0.83), deeming it safe for continued experiments. In the second experiment, we are currently assessing edema and behaviour 24 hours after moderate and severe ICH (n=10). No difference was found in brain water content (edema) measurements (p=0.361), conflicting with published pre-clinical literature in severe ischemic stroke. Additionally, glibenclamide did not improve neurological impairments (p= 0.40) or forelimb placing responses (p<0.4). This may be due to differences in edema formation and ionic regulation between the two stroke subtypes, and suggests that glibenclamide acts differently following ischemic and hemorrhagic stroke.
Poster
Authors & Affiliations
Tiffany F. C. Kung (Neuroscience and Mental Health Institute, University of Alberta), Cassandra M. Wilkinson (Psychology Department, University of Alberta), Fred Colbourne (Psychology Department, University of Alberta)