Related Experiment Video
Updated: Mar 22, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Lithium Treatment Prevents Apoptosis in Neonatal Rat Hippocampus Resulting from Sevoflurane Exposure
Xue Zhou1, Wen- da Li2, Bao-Long Yuan1
1Department of Anaesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, People's Republic of China.
Insights
Lithium protects the immature brain hippocampus from anesthetic sevoflurane-induced damage. This study shows lithium’s therapeutic potential in mitigating neurotoxicity and improving learning and memory deficits following sevoflurane exposure.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Neonatal exposure to general anesthetics like sevoflurane can cause long-term neurodevelopmental issues.
- The hippocampus is particularly vulnerable to anesthetic-induced apoptosis and cognitive impairment.
- Glycogen synthase kinase-3 beta (GSK-3β) pathway is implicated in neuronal apoptosis and plasticity.
Purpose of the Study:
- To investigate the neuroprotective effects of lithium chloride against sevoflurane-induced apoptosis in the immature rat hippocampus.
- To explore the role of the GSK-3β pathway in sevoflurane neurotoxicity and lithium's modulatory effect.
- To assess the impact of sevoflurane exposure and lithium treatment on learning and memory in juvenile rats.
Main Methods:
- Postnatal Sprague-Dawley rat pups were administered lithium chloride or saline, followed by sevoflurane or air exposure.
- Western blot analysis was used to measure cleaved caspase-3, nNOS, GSK-3β, and p-GSK-3β protein levels.
- Histopathological examination (Nissl and TUNEL staining) and behavioral tests (radial arm maze, step-through test) were performed.
Main Results:
- Sevoflurane exposure induced caspase-3 activation and hippocampal histopathological damage, which were attenuated by lithium chloride.
- Sevoflurane increased GSK-3β activity, while lithium pretreatment decreased it.
- Lithium treatment showed potential therapeutic effects on spatial learning and memory deficits induced by sevoflurane.
Conclusions:
- Lithium attenuates sevoflurane-induced neonatal hippocampal damage, likely through modulation of the GSK-3β pathway.
- Lithium may offer a therapeutic strategy to counteract the neurotoxic effects of sevoflurane and improve cognitive function after neonatal exposure.
Abstract:
We aimed to observe the therapeutic effects of lithium on inhalational anesthetic sevoflurane-induced apoptosis in immature brain hippocampus. From postnatal day 5 (P5) to P28, male Sprague-Dawley pups were intraperitoneally injected with lithium chloride or 0.9 % sodium chloride. On P7 after the injection, pups were exposed to 2.3 % sevoflurane or air for 6 h. Brain tissues were harvested 12 h and 3 weeks after exposure. Cleaved caspase-3, nNOS protein, GSK-3β,p-GSK-3β were assessed by Western blot, and histopathological changes were assessed using Nissl stain and TUNEL stain. From P28, we used the eight-arm radial maze test and step-through test to evaluate the influence of sevoflurane exposure on the learning and memory of juvenile rats. The results showed that neonatal sevoflurane exposure induced caspase-3 activation and histopathological changes in hippocampus can be attenuated by lithium chloride. Sevoflurane increased GSK-3β activity while pretreatment of lithium decreased GSK-3β activity. Moreover, sevoflurane showed possibly slight but temporal influence on the spatial learning and the memory of juvenile rats, and chronic use of lithium chloride might have the therapeutic effect. Our current study suggests that lithium attenuates sevoflurane induced neonatal hippocampual damage by GSK-3β pathway and might improve learning and memory deficits in rats after neonatal exposure.
