Grant: CIHR Fellowship

Brain swelling is a major cause of mortality following insults such as stroke and traumatic brain injury. This condition is often caused by an underlying swelling of neurons in the brain, leading to cell death. We currently have limited capacity to replace these neurons, and therefore must devise strategies to reduce the swelling-induced cell death. Recent evidence suggests that an ion channel protein, called Panx1, is involved in this process. Ion channels act essentially as conduits between cells and the external environment. These proteins pass important signalling molecules to co-ordinate cellular responses, such as cell growth, movement, or death. In this project, I will test whether Panx1 conduits promote cell death following neuronal swelling. I will also examine the mechanisms through which Panx1 channels are activated during neuronal swelling. Early experiments indicate that harmful molecules known as reactive oxygen species, which are created within swollen cells, might play a role in this Panx1 activation and neuron death. Reactive oxygen species cause damage to all cellular components, including proteins. Therefore I will also examine whether these molecules activate Panx1 conduits by modifying parts of the protein structure. This work contributes to unraveling the complex and still largely unknown mechanisms underlying neuronal swelling and death, and will guide future studies on therapeutic interventions for brain edema and neuronal death.