Editing Delirium (section)

===Animal models===
The lack of animal models that are relevant to delirium has left many key questions in delirium pathophysiology unanswered. Earliest rodent models of delirium used [[atropine]] (a [[muscarinic acetylcholine receptor]] blocker) to induce cognitive and electroencephalography (EEG) changes similar to delirium, and other [[anticholinergic]] drugs, such as [[biperiden]] and [[hyoscine]], have produced similar effects. Along with clinical studies using various drugs with anticholinergic activity, these models have contributed to a "cholinergic deficiency hypothesis" of delirium.<ref>{{cite journal | vauthors = Hshieh TT, Fong TG, Marcantonio ER, Inouye SK | title = Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 63 | issue = 7 | pages = 764–772 | date = July 2008 | pmid = 18693233 | pmc = 2917793 | doi = 10.1093/gerona/63.7.764 }}</ref>

Profound systemic inflammation occurring during [[sepsis]] is also known to cause delirium (often termed sepsis-associated encephalopathy).<ref>{{cite journal | vauthors = Zampieri FG, Park M, Machado FS, Azevedo LC | title = Sepsis-associated encephalopathy: not just delirium | journal = Clinics | volume = 66 | issue = 10 | pages = 1825–1831 | date = 2011 | pmid = 22012058 | pmc = 3180153 | doi = 10.1590/S1807-59322011001000024 }}</ref> Animal models used to study the interactions between prior degenerative disease and overlying systemic inflammation have shown that even mild systemic inflammation causes acute and transient deficits in working memory among diseased animals.<ref name="Cunningham 2012">{{cite journal | vauthors = Cunningham C, Maclullich AM | title = At the extreme end of the psychoneuroimmunological spectrum: delirium as a maladaptive sickness behaviour response | journal = Brain, Behavior, and Immunity | volume = 28 | pages = 1–13 | date = February 2013 | pmid = 22884900 | pmc = 4157329 | doi = 10.1016/j.bbi.2012.07.012 }}</ref> Prior [[dementia]] or age-associated cognitive impairment is the primary predisposing factor for clinical delirium and "prior pathology" as defined by these new animal models may consist of synaptic loss, abnormal network connectivity, and "primed [[microglia]]" brain macrophages stimulated by prior neurodegenerative disease and aging to amplify subsequent inflammatory responses in the [[central nervous system]] (CNS).<ref name="Cunningham 2012" />