Fig. 3

The mechanism of excitotoxicity. The sustained activation of N-methyl-D aspartate receptors (NMDAR) due to excessively high concentrations of glutamate (Glu) results in a substantial influx of calcium into the cell. This influx, in turn, triggers the activation of lytic enzymes and nitric oxide synthase (NOS). Concurrently, heightened levels of arachidonic acid and mitochondrial impairment foster the generation of reactive oxygen species, initiating a cascade of biomolecular damage. Ultimately, these processes lead to the activation of apoptotic death programs within cells. The impact of energy shortages compounds the degenerative process. Energy deficits prolong membrane depolarization by impairing the energy supply to the sodium/potassium pump (Na/K ATPase). This, in turn, maintains NMDAR in an active state, rendering the cell more susceptible to the typical glutamatergic inputs from the cerebral cortex. Adapted from Lorigados et al [38]