Table 2.

Selected animal studies investigating post-ARDS cognitive impairment

Author(s)	Year	Animal model	Results/conclusions
De la Torre et al.	1992	Rat	Chronic cerebrovascular insufficiency following ligation of the common carotid and left subclavian arteries in aged rats induces behavioral and cognitive impairments consistent with dementia
Pappas et al.	1996	Rat	Rats exposed to chronic reduction of cerebral blood flow following carotid artery ligation develop memory dysfunction and cell loss in the CA1 region of the hippocampus
Feldman et al.	1997	Rabbit	Positive end-expiratory pressure reduces intracranial compliance in rabbits
Wilson et al.	2003	Mouse	High-tidal-volume mechanical ventilation upregulates cytokines in mouse lungs
Altmeier et al.	2005	Mouse	Systemic inflammation simulated by lipopolysaccharide in mechanically ventilated mice induces cytokine-mediated lung injury in mechanically ventilated wild-type mice
Fries et al.	2005	Pig	Mechanically ventilated pigs exposed to hypoxemia with lung injury develop histopathologic changes in the CA1 region of the hippocampus not when exposed to the same degree of hypoxemia alone, suggesting lung injury as a mechanism of damage independent from hypoxemia
Semmler et al.	2005	Rat	Systemic inflammation induces apoptosis in the rat brain, particularly in the hippocampus
Wilson et al.	2005	Mouse	Pulmonary inflammation following high-tidal-volume mechanical ventilation in mice without underlying lung injury is mediated by TNF-α
Bickenbach et al.	2009	Pig	Low- versus high-tidal-volume mechanical ventilation improves cerebral tissue oxygenation in pigs
Wolthuis et al.	2009	Mouse	Mechanical ventilation even at lower tidal volumes causes lung injury in wild-type mice without history of lung disease
Bickenbach et al.	2011	Pig	Mechanically ventilated pigs exposed to hypoxemia with lung injury demonstrate trends toward elevated cytokines IL-6 and TNF-α in the CA1 region of the hippocampus versus mechanically ventilated pigs exposed to hypoxemia alone
Heuer et al.	2011	Pig	In mechanically ventilated pigs, ARDS results in elevations in TNF-α, IL-6, and IL-1β, which further increase in pigs with acute intracranial hypertension. The combination of ARDS and acute intracranial hypertension results in hippocampal damage. Acute intracranial hypertension induces lung injury and extravascular lung water
Imamura et al.	2011	Mouse	In a mouse model of septic encephalopathy, an IL-1β cytokine-mediated process disrupts the synaptic processing of long-term potentiation in the hippocampus
Davis et al.	2015	Mouse	Baseline neurodegeneration in mice increases the risk, duration, and severity of delirium
Shohami et al.	2016	Rat	TNF-α and IL-6 are detected in the contused hemisphere of rats soon after closed head injury, but not in healthy rats. TNF-α is detected as early as 1 h after injury and peaks at 4 h, whereas IL-6 is detected at 3–5 h and peaks at 8 h after injury
Lahiri et al.	2019	Mouse	High-tidal-volume mechanical ventilation simulates Alzheimer’s disease pathophysiology in transgenic Alzheimer’s disease and wild-type mice