title: Role of microglia and toll-like receptor 4 in the pathophysiology of delirium.
abstract: Delirium is a serious medical condition that commonly afflicts elderly inpatients. This is especially common in the post-operative setting where it increases mortality, length of hospital stay and health care costs. The exact mechanisms involved in its pathogenesis remain uncertain and there is currently no effective pharmacological therapy for treatment or prevention of delirium. We hypothesize that microglia-mediated neuroinflammation via toll-like receptor 4 signalling is a significant contributor to post-operative delirium. Based on our proposed mechanism, three novel pharmacological therapies have been suggested to be effective to prevent or treat delirium. Curcumin, ibudilast and minocycline have been shown to interfere with various steps in the proinflammatory microglial activation intracellular signalling pathway, disrupting the subsequent neuroinflammatory cascade. We hypothesize that these drugs could be a novel pharmacotherapy that could significantly improve the outcome of post-operative delirious patients.
authors.affiliation: Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, Australia.
authors.forename: Ryan
authors.initials: R
authors.lastname: Jalleh
authors.forename: Keith
authors.initials: K
authors.lastname: Koh
authors.forename: Boyoun
authors.initials: B
authors.lastname: Choi
authors.forename: Ebony
authors.initials: E
authors.lastname: Liu
authors.forename: John
authors.initials: J
authors.lastname: Maddison
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hutchinson
mesh_terms: D000368:Aged; D003693:Delirium / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged; D008962:Models, Theoretical; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4