Role of microglia and toll-like receptor 4 in the pathophysiology of delirium |
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| Affiliation: | 1. Division of Geriatrics, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA;2. Geriatrics, Palliative, and Extended Care Service Line, San Francisco Veterans Affairs Medical Center, 4150 Clement Street (181G), San Francisco, CA 94121, USA;3. The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Department of Internal Medicine, B424 Starling Loving Hall 320 W 10th Avenue, Columbus, OH 43214, USA;4. James P. Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, USA;5. Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero St, Box 1770, San Francisco, CA 94403, USA |
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| 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. |
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