Project Title: Human cell-type specific ion dynamics in neuroinflammation and seizures
Host Organisation: University of Cape Town, South Africa
Ion gradients are a fundamental component of the nervous system. They are established by ion pumps, transporters and channels within cell membranes. Ion regulatory mechanisms often differ between cell types and changes in intracellular ion concentration have been implicated in multiple disease processes in the brain, with epilepsy being a prime example. This proposal focuses upon two key ions: chloride and hydrogen, which can exhibit intracellular changes over a range of timescales that have been linked to the development of epileptic seizures. Epilepsy is a debilitating disease which negatively impacts the health and wellbeing of approximately 50 million people worldwide. Epilepsy is especially common in Africa where most cases result from brain inflammation caused by head injuries or infection. How brain inflammation affects chloride and hydrogen ion gradients, and hence susceptibility to seizures is not known. To shed light on this important area, we will capitalise upon methods I have helped develop for directly measuring and manipulating ion concentrations within the nervous system. We will prepare human brain slice cultures from brain tissue, which has been resected during neurosurgical procedures and donated to a tissue bank. Utilising this valuable tissue we will measure and manipulate ion dynamics during brain inflammation using optical reporters and light-activated proteins. This research will determine how brain inflammation affects seizure development by modifying the concentration of chloride and hydrogen ions within brain cells. Our findings have the potential to inform the development of new treatments for epilepsy.