title: Long-lasting protection in brain trauma by endotoxin preconditioning.
abstract: We investigated the occurrence of endotoxin (lipopolysaccharide, LPS) preconditioning in traumatic brain injury (TBI), evaluating the time window of LPS-induced protection, its persistence, and the associated molecular mechanisms. Mice received 0.1 mg/kg LPS or saline intraperitoneally and subsequently TBI (by controlled cortical impact brain injury) at various time intervals. Mice receiving LPS 3, 5, or 7 days before TBI showed attenuated motor deficits at 1 week after injury compared with mice receiving saline. Those receiving LPS 5 days before injury had also a reduced contusion volume (7.9±1.3 versus 12±2.3 mm(3)) and decreased cell death. One month after injury, the protective effect of LPS on contusion volume (14.5±1.2 versus 18.2±1.2 mm(3)) and neurologic function was still present. Traumatic brain injury increased glial fibrillary acidic protein, CD11b, CD68, tumor necrosis factor-α, interleukin (IL)-10, and IL-6 mRNA expression 24 hours after injury. Lipopolysaccharide administered 5 (but not 9) days before injury increased the expression of CD11b (233%) and of interferon β (500%) in uninjured mice, while it reduced the expression of CD68 (by 46%) and increased that of IL-6 (by 52%) in injured mice. Lipopolysaccharide preconditioning conferred a long-lasting neuroprotection after TBI, which was associated with a modulation of microglia/macrophages activity and cytokine production.
authors.affiliation: Department of Anesthesia and Critical Care Medicine, University of Milano, Neurosurgical Intensive Care Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Longhi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Gesuete
authors.forename: Carlo
authors.initials: C
authors.lastname: Perego
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ortolano
authors.forename: Noemi
authors.initials: N
authors.lastname: Sacchi
authors.forename: Pia
authors.initials: P
authors.lastname: Villa
authors.forename: Nino
authors.initials: N
authors.lastname: Stocchetti
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: De Simoni
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D003071:Cognition / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*
chemical_list: D008070:Lipopolysaccharides; D018696:Neuroprotective Agents