Korean J Anesthesiol.  2019 Apr;72(2):169-177. 10.4097/kja.d.18.00005.

Dexmedetomidine and propofol sedation requirements in an autistic rat model

• Elmorsy SA
• Soliman GF
• Rashed LA
• Elgendy H

• KMID: 2447512
• DOI: http://doi.org/10.4097/kja.d.18.00005

Abstract

BACKGROUND
Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms.
METHODS
Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed.
RESULTS
Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats.
CONCLUSIONS
This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.

Keyword

Autism; Dexmedetomidine; GABA(A); Glutamate; Propofol

MeSH Terms

Adult
Animals
Autistic Disorder
Child
Dexmedetomidine*
Electroencephalography
Female
gamma-Aminobutyric Acid
Gene Expression
Glutamic Acid
Humans
Infant, Newborn
Male
Models, Animal*
N-Methylaspartate
Neurodevelopmental Disorders
Propofol*
Rats*
Rats, Sprague-Dawley
Receptors, GABA-A
Receptors, Glutamate
Reflex, Righting
Valproic Acid
Dexmedetomidine
Glutamic Acid
N-Methylaspartate
Propofol
Receptors, GABA-A
Receptors, Glutamate
Valproic Acid
gamma-Aminobutyric Acid