Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons

Abstract

Background:Propofol and etomidate are the most important intravenous general anesthetics in the current clinical use and that mediate gamma-aminobutyric acid's (GABAergic) synaptic transmission. However, their long-term effects on GABAergic synaptic transmission induced by neonatal propofol or etomidate exposure remain unclear. We investigated the long-term GABAergic neurotransmission alterations, following neonatal propofol and etomidate administration.Methods:Sprague-Dawley rat pups at postnatal days 4–6 were underwent 6-h-long propofol-induced or 5-h-long etomidate-induced anesthesia. We performed whole-cell patch-clamp recording from pyramidal cells in the cornus ammonis 1 area of acute hippocampal slices of postnatal 80–90 days. Spontaneous and miniature inhibitory GABAergic currents (spontaneous inhibitory postsynaptic currents [sIPSCs] and miniature inhibitory postsynaptic currents [mIPSCs]) and their kinetic characters were measured. The glutamatergic tonic effect on inhibitory transmission and the effect of bumetanide on neonatal propofol exposure were also examined.Results:Neonatal propofol exposure significantly increased the frequency of mIPSCs (from 1.87 ± 0.35 Hz to 3.43 ± 0.51 Hz, P < 0.05) and did not affect the amplitude of mIPSCs and sIPSCs. Both propofol and etomidate slowed the decay time of mIPSCs kinetics (168.39 ± 27.91 ms and 267.02 ± 100.08 ms vs. 68.18 ± 12.43 ms; P < 0.05). Bumetanide significantly blocked the frequency increase and reversed the kinetic alteration of mIPSCs induced by neonatal propofol exposure (3.01 ± 0.45 Hz and 94.30 ± 32.56 ms).Conclusions:Neonatal propofol and etomidate exposure has long-term effects on inhibitory GABAergic transmission. Propofol might act at pre- and post-synaptic GABA receptor A (GABAA) receptors within GABAergic synapses and impairs the glutamatergic tonic input to GABAergic synapses; etomidate might act at the postsynaptic site.

Neonatal phenobarbital exposure disrupts GABAergic synaptic maturation in rat CA1 neurons

“…32 Interestingly, etomidate exposure during the same period (i.e., P4-P6) does not induce long-term alterations in IPSC frequency. 33 Collectively, these data, along with our current experiments suggest that not all GABA-acting agents produce equivalent profiles of developmental disruption. The case of etomidate is particularly interesting, as the degree to which it induces apoptosis during brain development is unknown.…”

Etomidate Modulates the Tactile Stimulation-Evoked Field Potential Responses in Cerebellar Granule Cell Layer in vivo in Mice

“…In rat spinal dorsal horn neurons, ET at 10 μmol/L potentiated GABA current and slowed activation, desensitization, and deactivation of GABA A receptors; while ET at 10-1,000 μmol/L directly activated and desensitized GABA A receptors [1]. In hippocampal pyramidal cells, ET slowed the decay time of miniature inhibitory postsynaptic currents kinetics [9]. The ET inhibited thalamocortial relay neurons activity by potentiation of both synaptic and extrasynaptic GABA A receptors [10].…”

Propofol and sevoflurane combined with remifentanil on the pain index, inflammatory factors and postoperative cognitive function of spine fracture patients

“…Waterloo et al ( 11 ) found that fracture orthopedic surgery can cause damage to some soft tissues, leading to endothelial cell infiltration, producing inflammatory response; reducing the inflammatory response during operation can significantly increase the success rate of operation and improve the prognosis of patients. Zhang et al ( 12 ) showed that the propofol-induced anesthesia can significantly reduce the inflammatory response of patients during operation, obviously inhibiting the release of inflammatory factors and reducing the infiltration of neutrophils and eosinophils. Postoperative cognitive impairment is a common neurological complication of patients after operation, which often occurs in elderly patients, causing serious damage to the memory, attention and orientation of patients, and even affecting the life quality of patients after operation ( 13 ).…”