Etomidate-induced myoclonus correlates with the dysfunction of astrocytes and glutamate transporters in the neocortex of Sprague-Dawley rats.

Abstract

Etomidate-induced myoclonus is common in clinical anesthesia. Propofol and lidocaine, as other sedative hypnotic and anticonvulsant drugs, rarely induce myoclonus. The mechanism of the myoclonus remains unclear. Eighty-four adult male Sprague-Dawley (SD) rats anesthetized intravenously with etomidate, propofol, or lidocaine plus etomidate were observed of the behavioral changes at 0, 1, 2, 3, 4 and 5 min after anesthesia. Five minutes later, glutamate levels were measured in the cerebrospinal fluid (CSF), neocortex and hippocampus. The mRNAs and proteins expression of EAAT1, EAAT2, and GFAP in the neocortex and hippocampus were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunofluorescence staining. Etomidate increased the mean behavioral scores at different time points and the neocortical glutamate level compared with the propofol (p=0.0283) and the lidocaine plus etomidate group (p=0.0035); The correlation analysis revealed a strong correlation between the mean behavioral score and the neocortical glutamate content (Spearman's r=0.6638, p=0.0027). No significant difference was found in the EAAT1, EAAT2, or GFAP mRNAs in the neocortex and hippocampus among three groups; etomidate decreased EAAT1 (p=0.0416 and p=0.0127) and EAAT2 (p=0.0363 and p=0.0109) proteins but increased the GFAP (p=0.0145 and p=0.0149) protein in the neocortex compared to the propofol and lidocaine plus etomidate group. Furthermore, etomidate activated GFAP-positive cells in the neocortex, but conversely inhibited proteins of EAATs in motor cortex. Etomidate-induced myoclonus is associated with neocortical glutamate accumulation. Suppression of the astrogliosis in neocortex and promoting extracellular glutamate uptake by regulating glutamate transporters (EAATs) in the motor cortex may be the therapeutic target for prevention of etomidate-induced myoclonus.