Potential mechanisms and therapies for intensive care unit (ICU) delirium. Hypothesized mechanisms for ICU delirium include systemic inflammation, endothelial dysfunction, increased blood–brain barrier (BBB) permeability, and reduced cholinergic control of the inflammatory response that, along with baseline patient vulnerability factors, predispose patients to neuroinflammation and subsequent neuronal injury. Primed and overactivated microglia from these processes may also exacerbate the pathophysiologic changes. Therapeutic agents studied for the prevention or treatment of ICU delirium have targeted these pathways.