title: Microcirculatory dysfunction in the brain precedes changes in evoked potentials in endotoxin-induced sepsis syndrome in rats.
abstract: BACKGROUND
  During sepsis progression microcirculatory dysfunction precedes macrocirculatory failure, partly explaining the occurrence of early organ dysfunction. The matter concerning microcirculatory dysfunction in the brain under septic conditions is less clear. We investigated the integrity of the activation flow coupling during sepsis progression in a rat model of septic shock.
  
  
  METHODS
  Chloralose-anesthetized rats (n = 30) were subjected to electric forepaw stimulation. Over the somatosensory cortex electrical activity and hemodynamic responses were recorded with surface electrodes and laser Doppler. After baseline recordings, vehicle, 1 or 5 mg/kg lipopolysaccharide (LPS) from Escherichia coli was given intravenously, and activation flow coupling, blood pressure and blood gases were investigated at regular time points up to 270 min. In the end lactate, glucose, neuron-specific enolase (NSE) and S-100B protein levels were measured.
  
  
  RESULTS
  Besides stable data from the control group, all LPS-treated rats developed signs of septic shock, which were more pronounced in the 5 mg/kg LPS group. Cerebral hyperemia occurred and was similar between the sepsis groups despite lower blood pressure levels in the 5 mg/kg LPS group. While the activation flow coupling remained intact in the 1 mg/kg LPS group, an uncoupling occurred in the 5 mg/kg group. First, the evoked flow velocity responses dropped 60 min after sepsis induction before the somatosensory amplitudes also decreased 120 min later. From similar NSE levels we suggest a functional rather than structural deficit explaining the difference in evoked potentials.
  
  
  CONCLUSIONS
  For the first time we demonstrate microcirculatory dysfunction in the activation flow coupling of the brain. Inappropriate blood supply of neurons might explain the disturbance of neuronal function.
authors.affiliation: Department of Neurology, Justus-Liebig University Giessen, Giessen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Rosengarten
authors.forename: Mirko
authors.initials: M
authors.lastname: Hecht
authors.forename: Dieter
authors.initials: D
authors.lastname: Auch
authors.forename: Hossein Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.forename: Ralf Theo
authors.initials: RT
authors.lastname: Schermuly
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaps
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory; D006614:Hindlimb / Q000294:innervation; D006940:Hyperemia / Q000503:physiopathology; D019344:Lactic Acid / Q000097:blood; D017078:Laser-Doppler Flowmetry; D008070:Lipopolysaccharides; D008297:Male; D008833:Microcirculation; D009414:Nerve Growth Factors / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011897:Random Allocation; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D019344:Lactic Acid; D010751:Phosphopyruvate Hydratase