Fig. 5.
Dexmedetomidine reduces the excessive function of extrasynaptic α5 γ-aminobutyric acid type A (GABAA) receptors in neurons after general anesthesia and thereby prevents delirium. Dexmedetomidine activates α2 adrenergic receptors expressed in astrocytes and increases the level of phosphorylated extracellular signal–regulated kinase (p-ERK). These events stimulate the release of brain-derived neurotrophic factor (BDNF), which acts as a paracrine factor to stimulate tropomyosin receptor kinase B (TrkB) receptors expressed in neurons. Activation of TrkB receptors reduces cell-surface expression of extrasynaptic α5 GABAA receptors in neurons and thereby prevents deficits in memory and problem-solving after general anesthesia.