Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Oct 2014
Characterization of a double-hit murine model of acute respiratory distress syndrome.
The aim of the present study was to characterize a murine model of acute respiratory distress syndrome (ARDS) abiding by the Berlin definition of human ARDS and guidelines for animal models of ARDS. To this end, C57BL/6NCrl mice were challenged with lipopolysaccharide (LPS; 15 mg/kg, i.p.) followed 18 h later by injection of oleic acid (OA; 0.12 mL/kg, i.v.). Controls received saline injection at both time points. ⋯ The lung wet : dry ratio indicated damage to the alveolar capillary membrane. Cytokine patterns evidenced a severe local and systemic inflammatory state in plasma and lung tissue. In conclusion, the described two-hit model of ARDS shows a pathological picture of ARDS closely mimicking human ARDS according to the Berlin definition and may facilitate interpretation of prospective experimental results.
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Clin. Exp. Pharmacol. Physiol. · Oct 2014
Comparative StudyComparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease.
Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's disease (AD) requires an animal model that develops age-related cognitive deficits reproducibly between independent groups of investigators. Herein we assessed comparative temporal changes in spatial memory function in two commercially available transgenic mouse models of AD using the Morris water maze (MWM), incorporating both visible and hidden platform training. Individual cohorts of cDNA-based 'line 85'-derived double-transgenic mice coexpressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages of 3.6, 9.3 and 14.8 months. ⋯ In contrast, MWM studies with individual cohorts (aged 4-21 months) of single-transgenic genomic-based APPSwe mice expressing APPSwe on a yeast artificial chromosomal (YAC) construct showed no significant deficits in spatial memory acquisition until 21 months of age. There were no significant deficits in spatial memory retention up to 21 months of age and β-amyloid deposits were not present in brain sections up to 24 months of age. These data, generated using comprehensive study designs, show that APPSwe/PS1dE9 but not APPSwe YAC mice appear to provide a suitably robust model of AD for efficacy assessment of novel AD treatments in development.