fig5

Figure 5. Mechanistic depiction of neuron mitochondria with ketamine, glutamate, diazoxide, and other second messengers and potential mechanisms of injury during hypothermic circulatory arrest. This picture depicts a neuron with intracellular, intramitochondrial, and nuclear potential mechanisms of injury during hypothermic circulatory arrest. Both ketamine and diazoxide have potential neuroprotective effects. Ketamine is depicted here as affecting the NMDA receptors and subsequent second messengers within cytosol. Diazoxide is depicted as acting on the mitochondrial membrane at the mitoK_ATP channel and Complex II. Both pathways eventually affect ROS within the mitochondria. Downstream effects of both pathways are also thought to involve mechanisms within the nucleus that lead to DNA changes and apoptosis. Exploration of positive synergism of these agents is one option for future directions in neuroprotection research^[149]. This figure was created by Mary Ann Wilson, PhD, and is used with her permission. A version of this figure was also previously published^[149]. This figure is used with permission from Elsevier (obtained December 7, 2023, license number 5683710387270). ROS: Reactive oxygen species; MitoK_ATP: mitochondrial K_ATP channel; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA: N-methyl-D-aspartate; Cyt C: cytochrome C; DNA: deoxyribonucleic acid; NO: nitric oxide free radical.