title: Minocycline but not tigecycline is neuroprotective and reduces the neuroinflammatory response induced by the superimposition of sepsis upon traumatic brain injury.
abstract: OBJECTIVE
  The development of sepsis in patients with traumatic brain injury increases mortality, exacerbates morphological and functional cerebral damage, and causes persistent neuroinflammation, including microglial activation. The administration of antibiotics possessing both antimicrobial and immunomodulatory activity might attenuate both sepsis and posttraumatic cerebral inflammation. We compared the potential therapeutic efficacy of two tetracyclines, minocycline and the newer generation tigecycline, on functional neurobehavioral impairment and regional histopathological damage in an experimental model of combined traumatic brain injury and sepsis.
  
  
  METHODS
  Prospective, experimental animal study.
  
  
  METHODS
  University Research Laboratory.
  
  
  METHODS
  Adult male Sprague-Dawley rats.
  
  
  METHODS
  Controlled cortical impact was used to induce traumatic brain injury and cecal ligation and puncture for sepsis. Immediately following injury, animals were treated with minocycline (45 mg/kg intraperitoneal), tigecycline (7.5 mg/kg intraperitoneal), or saline every 12 hours for 3 days.
  
  
  RESULTS
  The development of sepsis and cerebral inflammatory response were evaluated, respectively, by 1) growth of peritoneal microorganisms and clinical variables and 2) tumor necrosis factor-α expression in the perilesional cortex. To assess posttraumatic outcome, vestibulomotor and cognitive function were evaluated at different time points for 14 days post injury whereupon animals were killed and cerebral tissue analyzed for lesion volume, regional hippocampal (CA1/CA3) cell death, and microglial activation in the perilesional cortex, lesion core zone, and choroid plexus. Treatment with both antibiotics reduced microorganism growth, body weight loss, and mortality but had no effect on vestibulomotor or cognitive function. Minocycline alone attenuated postinjury cortical lesion volume, hippocampal CA3 neuronal cell loss, tumor necrosis factor-α expression, and the extent of microglial activation and infiltration.
  
  
  CONCLUSIONS
  The significantly heightened mortality caused by the superimposition of sepsis upon traumatic brain injury can be reduced by administration of both antibiotics but only minocycline can decrease the extent of cell death in selectively cortical and hippocampal brain regions, via, in part, a reduction in cerebral inflammation.
authors.affiliation: 1Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Firenze, Italy. 2Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Adembri
authors.forename: Valentina
authors.initials: V
authors.lastname: Selmi
authors.forename: Luca
authors.initials: L
authors.lastname: Vitali
authors.forename: Alessia
authors.initials: A
authors.lastname: Tani
authors.forename: Martina
authors.initials: M
authors.lastname: Margheri
authors.forename: Beatrice
authors.initials: B
authors.lastname: Loriga
authors.forename: Martina
authors.initials: M
authors.lastname: Carlucci
authors.forename: Daniele
authors.initials: D
authors.lastname: Nosi
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.forename: Angelo Raffaele
authors.initials: AR
authors.lastname: De Gaudio
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications*; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D018696:Neuroprotective Agents; D000078304:Tigecycline; D008911:Minocycline