Long-lasting protection in brain trauma by endotoxin preconditioning

Luca Longhi, Raffaella Gesuete, Carlo Perego, Fabrizio Ortolano, Noemi Sacchi, Pia Villa, Nino Stocchetti, Maria Grazia De Simoni

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1919-1929
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number9
Publication statusPublished - Sept 2011


  • Inflammation
  • neuroprotection
  • pathophysiology
  • preconditioning
  • traumatic brain injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology


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