Hyun Jung Lee, Hye Rim Cho, Minji Bang, Yeo Song Lee, Youn Jin Kim, Kyuha Chong
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引用次数: 0
Abstract
Objective: Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure.
Methods: This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted.
Results: A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment.
Conclusion: The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.
期刊介绍:
The Journal of Korean Neurosurgical Society (J Korean Neurosurg Soc) is the official journal of the Korean Neurosurgical Society, and published bimonthly (1st day of January, March, May, July, September, and November). It launched in October 31, 1972 with Volume 1 and Number 1. J Korean Neurosurg Soc aims to allow neurosurgeons from around the world to enrich their knowledge of patient management, education, and clinical or experimental research, and hence their professionalism. This journal publishes Laboratory Investigations, Clinical Articles, Review Articles, Case Reports, Technical Notes, and Letters to the Editor. Our field of interest involves clinical neurosurgery (cerebrovascular disease, neuro-oncology, skull base neurosurgery, spine, pediatric neurosurgery, functional neurosurgery, epilepsy, neuro-trauma, and peripheral nerve disease) and laboratory work in neuroscience.