Acta Neuropathologica

, Volume 119, Issue 6, pp 737–754 | Cite as

The neuroinflammatory hypothesis of delirium

  • Joaquim Cerejeira
  • Horácio Firmino
  • Adriano Vaz-Serra
  • Elizabeta B. Mukaetova-Ladinska


Delirium is a neuropsychiatric syndrome characterized by a sudden and global impairment in consciousness, attention and cognition. It is particularly frequent in elderly subjects with medical or surgical conditions and is associated with short- and long-term adverse outcomes. The pathophysiology of delirium remains poorly understood as it involves complex multi-factorial dynamic interactions between a diversity of risk factors. Several conditions associated with delirium are characterized by activation of the inflammatory cascade with acute release of inflammatory mediators into the bloodstream. There is compelling evidence that acute peripheral inflammatory stimulation induces activation of brain parenchymal cells, expression of proinflammatory cytokines and inflammatory mediators in the central nervous system. These neuroinflammatory changes induce neuronal and synaptic dysfunction and subsequent neurobehavioural and cognitive symptoms. Furthermore, ageing and neurodegenerative disorders exaggerate microglial responses following stimulation by systemic immune stimuli such as peripheral inflammation and/or infection. In this review we explore the neuroinflammatory hypothesis of delirium based on recent evidence derived from animal and human studies.


Dementia Central Nervous System Response Acute Systemic Inflammation Neuroinflammatory Change Brain Parenchymal Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We are grateful to Pedro Batista and Vasco Nogueira for critical reading of this manuscript and helpful comments. We would like to thank the anonymous reviewers for their useful and constructive comments, as well as Mrs. Alyson Goldwater and Mrs. Isabel Amoedo for secretarial support and editing the text. This work was supported by a BIAL (Porto, Portugal) grant to JC and Alzheimer Society (London, UK) award to EBM-L.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Joaquim Cerejeira
    • 1
    • 2
  • Horácio Firmino
    • 2
  • Adriano Vaz-Serra
    • 1
    • 2
  • Elizabeta B. Mukaetova-Ladinska
    • 3
  1. 1.Coimbra UniversityCoimbraPortugal
  2. 2.Serviço de PsiquiatriaHospitais da Universidade de CoimbraCoimbraPortugal
  3. 3.Institute for Ageing and HealthNewcastle UniversityNewcastle upon TyneUK

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