Cell wall-mediated neuronal damage in early sepsis

Carlos J. Orihuela, Sophie Fillon, S. Hope Smith-Sielicki, Karim C. El Kasmi, Geli Gao, Konstantinos Soulis, Avinash Patil, Peter J. Murray, Elaine I. Tuomanen

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Neuronal dysfunction can occur in the course of sepsis without meningitis. Sepsis-associated neuronal damage (SAND) was observed in the hippocampus within hours in experimental pneumococcal bacteremia. Intravascular challenge with purified bacterial cell wall recapitulated SAND. SAND persisted in PAFr -/- mice but was partially mitigated in mice lacking cell wall recognition proteins TLR2 and Nod2 and in mice overexpressing interleukin-10 (IL-10) in macrophages. Thus, cell wall drives SAND through IL-10-repressible inflammatory events. Treatment with CDP-choline ameliorated SAND, suggesting that it may be an effective adjunctive therapy to increase survival and reduce organ damage in sepsis.

Original languageEnglish (US)
Pages (from-to)3783-3789
Number of pages7
JournalInfection and immunity
Volume74
Issue number7
DOIs
StatePublished - Jul 2006

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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