Isoflurane Anesthesia’s Impact on Gene Expression Patterns of Rat Brains in an Ischemic Stroke Model
Author:
Shpetko Yana Y.1ORCID, Filippenkov Ivan B.1ORCID, Denisova Alina E.2, Stavchansky Vasily V.1, Gubsky Leonid V.23, Limborska Svetlana A.1ORCID, Dergunova Lyudmila V.1
Affiliation:
1. Laboratory of Human Molecular Genetics, National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, Moscow 123182, Russia 2. Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, Moscow 117997, Russia 3. Federal Center for the Brain and Neurotechnologies, Federal Biomedical Agency, Ostrovitianov Str. 1, Building 10, Moscow 117997, Russia
Abstract
Background: Ischemic stroke (IS) is one of the most severe brain diseases. Animal models with anesthesia are actively used to study stroke genomics and pathogenesis. However, the anesthesia-related gene expression patterns of ischemic rat brains remain poorly understood. In this study, we sought to elucidate the impact of isoflurane (ISO) anesthesia on the extent of ischemic brain damage and gene expression changes associated with stroke. Methods: We used the transient middle cerebral artery occlusion (tMCAO) model under long-term and short-term ISO anesthesia, magnetic resonance imaging (MRI), RNA sequencing, and bioinformatics. Results: We revealed that the volume of cerebral damage at 24 h after tMCAO was inversely proportional to the duration of ISO anesthesia. Then, we revealed hundreds of overlapping ischemia-related differentially expressed genes (DEGs) with a cutoff of >1.5; Padj < 0.05, and 694 and 1557 DEGs only under long-term and short-term anesthesia, respectively, using sham-operated controls. Concomitantly, unique DEGs identified under short-term anesthesia were mainly associated with neurosignaling systems, whereas unique DEGs identified under long-term anesthesia were predominantly related to the inflammatory response. Conclusions: We were able to determine the effects of the duration of anesthesia using isoflurane on the transcriptomes in the brains of rats at 24 h after tMCAO. Thus, specific genome responses may be useful in developing potential approaches to reduce damaged areas after cerebral ischemia and neuroprotection.
Funder
Russian Science Foundation
Subject
Genetics (clinical),Genetics
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