Traffic of leukocytes and cytokine up-regulation in the central nervous system in sepsis

Clarissa M. Comim, Márcia C. Vilela, Larissa S. Constantino, Fabrícia Petronilho, Franciele Vuolo, Norinne Lacerda-Queiroz, David H. Rodrigues, João Luiz Da Rocha, Antônio L. Teixeira, João Quevedo, Felipe Dal-Pizzol

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Purpose: To evaluate the effects of sepsis on brain microvasculature leukocyte rolling and adherence, myeloperoxidase (MPO) activity, cytokine and chemokine concentrations, and behavioral screening 6, 12, and 24 h after sepsis induction. Methods: C57BL/6 mice or Wistar rats underwent cecal ligation and perforation (CLP) or sham operation. At 6, 12, and 24 h after sepsis induction, intravital microscopy was performed in the mice brain microvasculature to evaluate leukocyte rolling and adherence. Animals were killed and had the brain removed to determine MPO activity and the levels of cytokines and chemokines. A behavioral screening was also performed in a separate cohort of animals. Blood-brain barrier (BBB) permeability and cytokines and chemokines were determined in different brain regions in Wistar rats. Results: There was a decrease in circulating leukocyte levels at 6, 12, and 24 h, an increase in rolling and adhesion of leukocytes in the brain microvasculature, followed by an increase in brain MPO activity. In addition, there was an increase in both brain cytokines and chemokines at different times. There was a decrease in the neuropsychiatric state muscle tone and strength only at 6 h, and a decrease in the autonomous function at 6 and 12 h. The pattern of brain cytokines and chemokines, and BBB permeability between the analyzed regions seemed to be similar with minor differences. Conclusions: During sepsis the brain's production of cytokines and chemokines is an early event and it seemed to participate both in central nervous system (CNS) dysfunction and BBB permeability alterations, reinforcing the role of brain inflammatory response in the acute CNS dysfunction associated with sepsis.

Original languageEnglish (US)
Pages (from-to)711-718
Number of pages8
JournalIntensive care medicine
Volume37
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Keywords

  • Brain microvasculature
  • Central nervous system
  • Delirium
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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