Anesthesia and analgesia
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Anesthesia and analgesia · Oct 2016
Dexmedetomidine-Induced Neuroapoptosis Is Dependent on Its Cumulative Dose.
Dexmedetomidine (DEX) has inherent neuroprotective properties that have been attributed to the activation of prosurvival kinases. However, the impact of supraclinical doses of DEX on neuroapoptosis and neuronal viability has not been determined. ⋯ Although DEX is neuroprotective at clinical doses, high cumulative doses and concentrations induce neuroapoptosis, in vivo and in vitro, respectively. Because the current dosing schedules used in humans yield plasma levels that are substantially below concentrations that induce neurotoxicity, low-dose DEX should not be neurotoxic and has the potential to be a neuroprotective adjuvant.
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Anesthesia and analgesia · Oct 2016
Synergistic Modulation of γ-Aminobutyric Acid Type A Receptor-Mediated Synaptic Inhibition in Cortical Networks by Allopregnanolone and Propofol.
The neuroactive steroid allopregnanolone (ALLO) is an endogenous allosteric modulator of γ-aminobutyric acid type A (GABAA) receptors. There is evidence that ALLO, at physiologically relevant concentrations, modulates GABAA receptor function in the cerebral cortex. The widely used anesthetic agent propofol and ALLO share a similar mode of molecular action. Here, we ask how GABAA receptor-mediated synaptic inhibition and action potential firing of neurons in cultured cortical slices are altered by either ALLO or propofol or by coapplying both agents. ⋯ In cortical neurons, GABAA receptor-mediated synaptic transmission is potentiated by ALLO and propofol in a synergistic manner, whereas the effects on spontaneous action potential activity appear additive. A coapplication of neurosteroids and propofol in general anesthesia and intensive care medicine may open new ways to reduce anesthetic dose requirements and, thus, avoid undesired anesthetic-induced side effects.