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This study investigates the effects of low-concentration sevoflurane on excitatory/inhibitory balance and autism-like behaviors in mice and children with autism.

February 26, 2026Drug Design Development and Therapy0 citationsOpen Access

Low-Dose Sevoflurane Restores Prefrontal Excitatory/Inhibitory Balance and Improves Autism-Like Social Behavior: A Preclinical and Pilot Clinical Study

HXHaiping Xu ZSZiwen Shi XGXinying Guo

Key Points

This study investigates the effects of low-concentration sevoflurane on excitatory/inhibitory balance and autism-like behaviors in mice and children with autism.
BTBR mice were exposed to 1% sevoflurane for 30 minutes daily, for 5 days each week during specific postnatal weeks.
Children with autism received 1% sevoflurane for 2 hours per session, 3-5 times in the first two weeks, followed by additional sessions over 12 weeks.
Behavioral assessments were conducted at baseline and after treatment using various standardized scales.
Restoration of excitatory/inhibitory balance and improved social interaction and memory was observed in BTBR mice.
In ASD patients, a statistically significant reduction of 4.7 points in CARS score was noted post-treatment.
61% of children displayed positive responses on the CGI-I scale, indicating improvement in social behavior.
Sevoflurane treatment primarily enhanced social impairments without notable adverse effects during follow-up.

Abstract

Background: Medications aimed at modulating excitatory/inhibitory (E/I) balance have shown promise in alleviating the behavioral manifestations of autism spectrum disorder (ASD). We therefore aimed to investigate the potential of low-concentration sevoflurane, a GABA A agonist, to modulate E/I balance and affect autism-like behavior deficit in BTBR mice and ASD patients. Methods: In the preclinical study, BTBR mice were exposed to 1% sevoflurane for 30 minutes daily, 5 days per week, from postnatal weeks 4 to 6. Behavioral and electrophysiological assessments were performed. In the clinical trial, ASD patients received 1% sevoflurane treatments for 2 hours per session, 3– 5 times during the first two weeks, followed by 2– 3 sessions per week for a total of 12 weeks. Assessments were conducted at baseline and the 14 th week. The primary outcomes were evaluated using the Childhood Autism Rating Scale (CARS) and Clinical Global Impressions-Improvement (CGI-I) scale, while secondary outcomes were assessed using the Autism Diagnostic Observation Schedule-2 (ADOS-2), Clinical Global Impression-Severity Scale (CGI-S), Autism Treatment Evaluation Checklist (ATEC), and Autism Behavior Checklist (ABC). Results: Our preclinical results demonstrated that repeated exposure to low-concentration sevoflurane restored E/I balance and improved social interaction and social memory without affecting repetitive behaviors. Accordingly, an open-label and single-arm clinical trial enrolled 20 ASD patients in Guangzhou Women and Children’s Medical Center. Significant reduction in CARS score of 4.7 points was observed between baseline and the end of treatment, which is both statistically and clinically significant. Additionally, 61% of ASD children demonstrated a positive response as measured by the CGI-I scale. Furthermore, analysis of secondary outcomes revealed that sevoflurane treatment primarily improved social impairments in ASD patients. Importantly, no significant safety concerns were observed during the one-year follow-up. Conclusion: Low-concentration sevoflurane shows promise as a novel therapeutic strategy for improving social deficits in ASD by modulating E/I balance. Trial Registration: Chinese Clinical trial Number: ChiCTR1900027459. Keywords: sevoflurane, autism, excitatory/inhibitory balance, social behavior

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