title: Moderate Peep After Tracheal Lipopolysaccharide Instillation Prevents Inflammation and Modifies the Pattern of Brain Neuronal Activation.
abstract: BACKGROUND
  Ventilatory strategy and specifically positive end-expiratory pressure (PEEP) can modulate the inflammatory response and pulmonary-to-systemic translocation of lipopolysaccharide (LPS). Both inflammation and ventilatory pattern may modify brain activation, possibly worsening the patient's outcome and resulting in cognitive sequelae.
  
  
  METHODS
  We prospectively studied Sprague-Dawley rats randomly assigned to undergo 3 h mechanical ventilation with 7 mL/kg tidal ventilation and either 2 cmH2O or 7 cmH2O PEEP after intratracheal instillation of LPS or saline. Healthy nonventilated rats served as baseline. We analyzed lung mechanics, gas exchange, lung and plasma cytokine levels, lung apoptotic cells, and lung neutrophil infiltration. To evaluate brain neuronal activation, we counted c-Fos immunopositive cells in the retrosplenial cortex (RS), thalamus, supraoptic nucleus (SON), nucleus of the solitary tract (NTS), paraventricular nucleus (PVN), and central amygdala (CeA).
  
  
  RESULTS
  LPS increased lung neutrophilic infiltration, lung and systemic MCP-1 levels, and neuronal activation in the CeA and NTS. LPS-instilled rats receiving 7 cmH2O PEEP had less lung and systemic inflammation and more c-Fos-immunopositive cells in the RS, SON, and thalamus than those receiving 2 cmH2O PEEP. Applying 7 cmH2O PEEP increased neuronal activation in the CeA and NTS in saline-instilled rats, but not in LPS-instilled rats.
  
  
  CONCLUSIONS
  Moderate PEEP prevented lung and systemic inflammation secondary to intratracheal LPS instillation. PEEP also modified the neuronal activation pattern in the RS, SON, and thalamus. The relevance of these differential brain c-Fos expression patterns in neurocognitive outcomes should be explored.
authors.affiliation: *Critical Care Center, Corporació Sanitària Parc Taulí, Institut Universitari Parc Taulí, Universitat Autònoma de Barcelona, Campus d' Excel·lència Internacional, Bellaterra †CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid ‡Institut d'Investigació i Innovació Parc Taulí (I3PT), Fundació Parc Taulí, Corporació Sanitària Parc Taulí, Universitat Autònoma de Barcelona, Campus d' Excel·lència Internacional, Bellaterra §Critical Patient Translational Research Group, Department of Anesthesiology, Intensive Care and Pain Management, Hospital Clínico Universitario, Instituto de Investigación Sanitaria (IDIS) Universidad de Santiago de Compostela, Santiago de Compostela ¶Research Unit, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria ||Psychopathology and Neuropsychology Research Unit, Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Campus d' Excel·lència Internacional, Bellaterra #Psychopathology and Neuropsychology Research Unit, Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Campus d' Excel·lència Internacional, Bellaterra **Department of Respiratory Care, Massachusetts General Hospital ¶Department of Anesthesiology, Harvard University, Boston, Massachusetts.
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Quilez
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodríguez-González
authors.forename: Marc
authors.initials: M
authors.lastname: Turon
authors.forename: Sol
authors.initials: S
authors.lastname: Fernandez-Gonzalo
authors.forename: Jesús
authors.initials: J
authors.lastname: Villar
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kacmarek
authors.forename: Ma Nieves
authors.initials: MN
authors.lastname: Gómez
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Oliva
authors.forename: Lluís
authors.initials: L
authors.lastname: Blanch
authors.forename: Josefina
authors.initials: J
authors.lastname: López-Aguilar
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000503:physiopathology*; D005786:Gene Expression Regulation; D007118:Immunoassay; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000503:physiopathology* / Q000517:prevention & control; D008070:Lipopolysaccharides; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D011175:Positive-Pressure Respiration; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos