Overall, these results support a possible physiological role for Aβ1-40 to decrease BBB permeability and neuronal injury during the acute stress of MV, however it is expected that long-term sustained of this putative protective pathway will contribute to neurodegeneration and cognitive impairment.ġFederal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia 2Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology N.V. There was increased distribution of Aβ1-40 in regions of acute vascular disruption, resulting in lower BBB permeability. BBB permeability and neuronal injury were decreased in mechanically ventilated ADtg mice, whereas BBB permeability and neuronal injury were increased in mechanically ventilated WT mice compared to their respective SB controls. Short-term MV resulted in increased cerebral soluble Aβ1-40 and increased cerebral TNF-α and IL-6 concentrations. Immunohistochemistry was used to assess the regional relationship between amyloid-β1–40 and acute vascular disruption and neuronal injury. Hippocampal blood-brain barrier permeability was quantified using a novel methodology that enabled assessment of small and large molecule permeability across the blood-brain barrier. Cerebral soluble/insoluble amyloid-β (Aβ) and neurological and systemic markers of inflammation were quantified. We subjected double transgenic Alzheimer’s disease (Adtg) (APP/PSEN1) and wild-type (WT) mice to MV for 4 hours and compared to spontaneously breathing (SB) controls. Mechanical ventilation (MV) is a hallmark critical care intervention that is strongly associated with cognitive decline. 1Cedars-Sinai Medical Center, Neurocritical Care, Los Angeles, United States 2Cedars-Sinai Medical Center, Departments of Neurology, Neurosurgery, and Biomedical Sciences, Los Angeles, United StatesĪ long-term cognitive impairment that resembles Alzheimer’s disease (AD) is a known complication of acute critical illnesses that affects up to 2 million individuals annually in the US.
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