Brain Maturation in Neonatal Rodents Is Impeded by Sevoflurane Anesthesia

Abstract

Background A wealth of data shows neuronal demise after general anesthesia in the very young rodent brain. Here we apply proton magnetic resonance spectroscopy (1HMRS), testing the hypothesis that neurotoxic exposure during peak synaptogenesis can be tracked via changes in neuronal metabolites. Methods 1HMRS spectra was acquired in the brain (thalamus) of neonatal rat pups 24- and 48 h after sevoflurane exposure on post-natal day (PND) 7 and 15, and in unexposed, sham controls. A repeated measure ANOVA was performed to examine if changes in metabolites were different between exposed and unexposed groups. Sevoflurane-induced neurotoxicity on PND7 was confirmed by immunohistochemistry. Results In unexposed PND7 pups (N=21), concentration of NAA ([NAA]) increased by 16% from PND8 to PND9, whereas in exposed PND7 pups (N=19), [NAA] did not change and concentration of choline compounds ([GPC+PCh]) decreased by 25%. In PND15 rats, [NAA] increased from PND16 to PND17 for both the exposed (N=14) and unexposed (N=16) groups. Two-way ANOVA for PND7 pups demonstrated changes over time observed in [NAA] (p=0.031) and [GPC+PCh] (p=0.024) were different between those two groups. Conclusions We demonstrated that normal [NAA] increase from PND8 to PND9 was impeded in sevoflurane-exposed rats when exposed at PND7; however, not impeded when exposed on PND15. Furthermore, we showed that non-invasive 1HMRS is sufficiently sensitive to detect subtle differences in developmental time trajectory of [NAA]. This is potentially clinically relevant since 1HMRS can be applied across species, and may be useful in providing evidence of neurotoxicity in the human neonatal brain.

Effects of hypotension and/or hypocapnia during sevoflurane anesthesia on perfusion and metabolites in the developing brain of piglets—a blinded randomized study

“…A decreased concentration of NAA may reflect neuronal dysfunction or neural death . Therefore, the group independent decrease in NAA may be due to neuronal effects of anesthesia itself, in accordance with previous studies performed in humans and mice . However, the decrease in NAA was more pronounced with HT.…”

Cistanches alleviates sevoflurane‐induced cognitive dysfunction by regulating PPAR‐γ‐dependent antioxidant and anti‐inflammatory in rats

“…3,6,7 Sevoflurane is commonly used in clinical anaesthesia for patients of all ages due to its low blood-gas partition coefficient and low metabolic breakdown. 9 Decreased connectivity between excitatory neurons in the prefrontal cortex has been shown to be correlated with cognitive impairments induced by sevoflurane. For example, Makaryus reported that sevoflurane has neurotoxic effects on the development of brain.…”

Neonatal sevoflurane exposure induces impulsive behavioral deficit through disrupting excitatory neurons in the medial prefrontal cortex in mice

“…Given the potential issue of public mental health and social stability, identifying the links between general anesthesia and impulse control disorder is now of paramount importance. Sevoflurane, the most commonly used pediatric anesthetic, has been shown to act as a neurotoxin affecting synaptogenesis and neuronal morphology in animal studies 12,13 . Therefore, we hypothesize that exposure of the immature brain to sevoflurane may induce ADHD-like behavior conditions in later adulthood.…”