Anesthetic Dose/Duration Model Main findings Reference
Sevoflurane 3%, 6 hours PD7 Sprague-Dawley rats Sevoflurane elevated caspase-3 activation and ROS levels, decreased mitochondrial cardiolipin contents, altered cellular ultrastructure in the cerebral cortex and metabolic pathways of glucose and intracellular antioxidants. Liu, et al.[109]
Ketamine 25 µM, 24 hours Hippocampal neuron cultures from 19-day-old Wistar rat embryos Ketamine exposure significantly increased the number of apoptotic neurons and the cytosolic calcium concentration. Ketamine also led to a down-regulation of the CaMKII and a decrease in synapsin. Sinner, et al.[51]
Sevoflurane 1.5%, 2 hours PD7 mouse pups Sevoflurane increased the phosphorylation of methyl-CpG island binding protein 2 in the hippocampus and sevoflurane-induced increases of neuronal cell death and phosphorylation of methyl-CpG were reversed by pre-treatment with memantine, a partial antagonist of the NMDAR Han, et al.[48]
Propofol 25 mg/kg, 1 dose PD14 Wistar rats Propofol induced a significant decrease in the level of nerve growth factor in the thalamus and altered the expression levels of a variety of key neurotrophic factor receptors and downstream targets such as Akt and Erk. Popic, et a. [60]
Midazolam/Nitrous Oxide/ Isoflurane 9 mg/kg midazolam, 75% NO, 0.75% iso, 6 hours PD7 Sprague-Dawley rats Anesthesia exposure up-regulated reactive oxygen species generation and down-regulated superoxide dismutase. Exposure to the anesthesia was also associated with increased mitochondrial fission. Boscolo, et al.[57]
Ketamine 100 µM, 24 hours Human stem cell-derived neurons Ketamine exposure increased neuronal apoptosis, ROS production, and mitochondrial fission, ketamine induces implicating mitochondrial dysfunction as a key mechanism by which neurotoxicity. Bai, et al.[45]
Isoflurane Surgical dose, 5 hours Fetal rhesus macaques Isoflurane induced a significant increase in apoptosis of neurons and oligodendrocytes in the fetal monkey brain. Creeley, et al.[110]
Table 1: The representative animal studies regarding anesthetic-induced developmental neurotoxicity