Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

Abstract

In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9–11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage.

A Randomised Trial: BIS-Guided Anesthesia Decreases The Incidence of Delayed Neurocognitive Recovery And Postoperative Neurocognitive Disorder But Not Postoperative Delirium

“…Deeper anesthesia means lower metabolic of the brain, which can increase the tolerance to ischemia and hypoxia, reducing the body's stress response [18] . These results were similar to the nding of Tasbihgou SR [30] that deepening anesthesia attenuated the brain changes associated with hypoxia in rats. These studies illustrate a deep anesthesia associated with inhibition of in ammation [31] and burst suppression may be the protective factors of POCD [32] .…”

Noninvasive Ultrasonic Drug Uncaging Maps Whole-Brain Functional Networks

“…To more fully assess the spatial profile of the anesthesia induced with ultrasonic propofol uncaging, we turned to functional brain imaging. Specifically, we used positron emission tomography (PET) imaging of the uptake of [18F]-fluorodeoxyglucose (FDG), a glucose analog, with a relative decrease in FDG avidity indicating effective anesthesia induced by the uncaged propofol (Tasbihgou et al, 2018). Given the low rate of diffusion for propofol within the brain (Gredell et al, 2004), the spatial extent of the anesthesia induced by ultrasonic propofol uncaging would be determined by the extent of parenchyma whose perfusion is supplied by the vessels in which the nanoparticles are uncaged.…”

Real-time telemetry monitoring of oxygen in the central complex of freely-walking Gromphadorhina portentosa

“…The mechanism by which simple molecules can induce anesthesia it is not yet well known but the prevailing hypotheses concern the modification of the lipid membrane fluidity and the interaction with the γ-Aminobutyric acid (GABA) A ionotropic receptor [47]. Modern anaesthetics are GABA A agonists, induce GABA-mediated neuronal hyperpolarization and, by causing a dose-dependent suppression of cerebral metabolism, reduce neural demand of oxygen and glucose [48]. Immunohistochemical staining confirmed the presence of GABA A receptors in insects [49].…”