Xenon neurotoxicity in rat hippocampal slice cultures is similar to isoflurane and sevoflurane.

BACKGROUND: Anesthetic neurotoxicity in the developing brain of rodents and primates has raised concern. Xenon may be a nonneurotoxic alternative to halogenated anesthetics, but its toxicity has only been studied at low concentrations, where neuroprotective effects predominate in animal models. An equipotent comparison of xenon and halogenated anesthetics with respect to neurotoxicity in developing neurons has not been made. METHODS: Organotypic hippocampal cultures from 7-day-old rats were exposed to 0.75, 1, and 2 minimum alveolar concentrations (MAC) partial pressures (60% xenon at 1.2, 2.67, and 3.67 atm; isoflurane at 1.4, 1.9, and 3.8%; and sevoflurane at 3.4 and 6.8%) for 6 h, at atmospheric pressure or in a pressure chamber. Cell death was assessed 24 h later with fluorojade and fluorescent dye exclusion techniques. RESULTS: Xenon caused death of hippocampal neurons in CA1, CA3, and dentate regions after 1 and 2 MAC exposures, but not at 0.75 MAC. At 1 MAC, xenon increased cell death 40% above baseline (P < 0.01; ANOVA with Dunnett test). Both isoflurane and sevoflurane increased neuron death at 1 but not 2 MAC. At 1 MAC, the increase in cell death compared with controls was 63% with isoflurane and 90% with sevoflurane (both P < 0.001). Pretreatment of cultures with isoflurane (0.75 MAC) reduced neuron death after 1 MAC xenon, isoflurane, and sevoflurane. CONCLUSION: Xenon causes neuronal cell death in an in vitro model of the developing rodent brain at 1 MAC, as does isoflurane and sevoflurane at similarly potent concentrations. Preconditioning with a subtoxic dose of isoflurane eliminates this toxicity.

Anesthetic protection of neurons injured by hypothermia and rewarming: roles of intracellular Ca2+ and excitotoxicity.

BACKGROUND: Mild hypothermia is neuroprotective after cerebral ischemia but surgery involving profound hypothermia (PH, temperature less than 18°C) is associated with neurologic complications. Rewarming (RW) from PH injures hippocampal neurons by glutamate excitotoxicity, N-methyl-D-aspartate receptors, and intracellular calcium. Because neurons are protected from hypoxia-ischemia by anesthetic agents that inhibit N-methyl-D-aspartic acid receptors, we tested whether anesthetics protect neurons from damage caused by PH/RW. METHODS: Organotypic cultures of rat hippocampus were used to model PH/RW injury, with hypothermia at 4°C followed by RW to 37°C and assessment of cell death 1 or 24 h later. Cell death and intracellular Ca were assessed with fluorescent dye imaging and histology. Anesthetic agents were present in the culture media during PH and RW or only RW. RESULTS: Injury to hippocampal CA1, CA3, and dentate neurons after PH and RW involved cell swelling, cell rupture, and adenosine triphosphate (ATP) loss; this injury was similar for 4 through 10 h of PH. Isoflurane (1% and 2%), sevoflurane (3%) and xenon (60%) reduced cell loss but propofol (3 µM) and pentobarbital (100 µM) did not. Isoflurane protection involved reduction in N-methyl-D-aspartate receptor-mediated Ca influx during RW but did not involve γ-amino butyric acid receptors or KATP channels. However, cell death increased over the next day. CONCLUSION: Anesthetic protection of neurons rewarmed from 4°C involves suppression of N-methyl-D-aspartate receptor-mediated Ca overload in neurons undergoing ATP loss and excitotoxicity. Unlike during hypoxia/ischemia, anesthetic agents acting predominantly on γ-aminobutyric acid receptors do not protect against PH/RW. The durability of anesthetic protection against cold injury may be limited.

Anesthetic Selection for an Awake Craniotomy for a Glioma With Wernicke's Aphasia: A Case Report.

Awake craniotomies for tumor resections allow for the preservation of eloquent cortex; however, they are high-risk surgeries that require careful patient selection and meticulous anesthetic management. Patients with significant preoperative language deficits may be unable to participate in intraoperative language mapping, increasing the risk of a failed surgery. Furthermore, anesthetic agents given for sedation and analgesia during the initial portion of the surgery may exacerbate existing language deficits. We present a case of an asleep-awake-asleep craniotomy for a left temporal lobe glioma using intraoperative neuronavigation, 5-aminolevulinic acid fluorescence, and awake speech mapping for a patient with a significant preoperative language deficit, for whom sedation had to be meticulously titrated to optimize intraoperative language testing. Anesthetic titration was aided by bispectral index monitoring, ultimately allowing successful awake speech mapping and tumor resection.

Effect of combining anesthetics in neonates on long-term cognitive function.

BACKGROUND: With growing evidence that anesthesia exposure in infancy affects cognitive development, it is important to understand how distinct anesthetic agents and combinations can alter long-term memory. Investigations of neuronal death suggest that combining anesthetic agents increases the extent of neuronal injury. However, it is unclear how the use of simultaneously combined anesthetics affects cognitive outcome relative to the use of a single agent. METHODS: Postnatal day 7 (P7) male rats were administered either sevoflurane as a single agent or the combined delivery of sevoflurane with nitrous oxide at 1 Minimum Alveolar Concentration for 4 h. Behavior was assessed in adulthood using the forced alternating T-maze, social recognition, and context-specific object recognition tasks. RESULTS: Animals exposed to either anesthetic were unimpaired in the forced alternating T-maze test and had intact social recognition. Subjects treated with the combined anesthetic displayed a deficit, however, in the object recognition task, while those treated with sevoflurane alone were unaffected. CONCLUSION: A combined sevoflurane and nitrous oxide anesthetic led to a distinct behavioral outcome compared with sevoflurane alone, suggesting that the simultaneous use of multiple agents may uniquely influence early neural and cognitive development and potentially impacts associative memory.