title: Cell wall-mediated neuronal damage in early sepsis.
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.
authors.affiliation: Infectious Diseases, St. Jude Children's Research Hospital, Mailstop 320 IRC 8057, 332 N. Lauderdale Rd., Memphis, TN 38105, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Orihuela
authors.forename: Sophie
authors.initials: S
authors.lastname: Fillon
authors.forename: S Hope
authors.initials: SH
authors.lastname: Smith-Sielicki
authors.forename: Karim C
authors.initials: KC
authors.lastname: El Kasmi
authors.forename: Geli
authors.initials: G
authors.lastname: Gao
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Soulis
authors.forename: Avinash
authors.initials: A
authors.lastname: Patil
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Murray
authors.forename: Elaine I
authors.initials: EI
authors.lastname: Tuomanen
mesh_terms: D000818:Animals; D002473:Cell Wall / Q000502:physiology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D011008:Pneumococcal Infections / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*