Mechanisms of neuroprotection and neurotoxicity associated with glutamate excitotoxicity in CNS neurons

This thesis investigated the mechanisms of neuroprotection and neurotoxicity in rat and human central nervous system (CNS) neurons. A brief literature review summarized the physiological and pathophysiological roles the excitatory neurotransmitter glutamate plays in the CNS. Many of the pathophysiological processes that occur during excitotoxic cell death are triggered by large increases in intracellular Ca2+ concentrations ([Ca2+]i). These pathophysiological processes were also described briefly. Chapter 2 described the development of the two primary neuronal cell culture models which were used for this study: the rat cerebellar granule cell culture model and the human foetal brain culture model (which consisted primarily of cortical neurons). The types of cells found in these cultures were characterised and immunohistochemical analysis showed that 75-80% of these cultures were neuronal. Conditions for a glutamate insult were established and under these conditions, 50% of the cells in both models were sensitive to glutamate and died within 48 hr of the glutamate insult, whereas 50% of the cells were resistant and were able to survive