Excitotoxic mechanisms in the hippocamus and cerebellum during brain ischemia

Brain ischemia triggers a two‑phase response that ultimately leads to neuronal injury. While much research has focused on the severe ionic disruption of the late phase, early ischemic events may also drive selective neuronal vulnerability. This dissertation investigates early and late ischemic mechanisms in both hippocampal CA1 neurons and cerebellar Purkinje cells. Purkinje cells depolarize to near 0 mV during ischemia, but unlike CA1 neurons, their ischemic depolarization is primarily driven by non‑desensitizing AMPA receptors and is reduced by extracellular calcium removal. Early increases in intracellular calcium in CA1 neurons occur independently of synaptic activity, whereas Purkinje cells do not exhibit the ischemia‑induced rise in miniature EPSCs seen in hippocampus. These regional differences reflect distinct synaptic architectures and reveal that ischemic responses vary substantially across brain areas. This work improves understanding of early ischemic events and highlights important differences in neuronal susceptibility throughout the brain.