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

• Published in: Intensive care medicine Vol. 37; no. 4; pp. 711 - 718
• Main Authors: Comim, Clarissa M., Vilela, Márcia C., Constantino, Larissa S., Petronilho, Fabrícia, Vuolo, Franciele, Lacerda-Queiroz, Norinne, Rodrigues, David H., da Rocha, João Luiz, Teixeira, Antônio L., Quevedo, João, Dal-Pizzol, Felipe
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2011; Springer; Springer Nature B.V
• Subjects: Analysis; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthesiology; Animal behavior; Animals; Behavior; Biological and medical sciences; Blood-brain barrier; Brain; Cecum; Central nervous system; Central Nervous System - metabolism; Central Nervous System - physiopathology; Chemokines; Critical Care Medicine; Cytokines; Cytokines - metabolism; Delirium; Emergency and intensive care: infection, septic shock; Emergency Medicine; Experimental; Infection; Inflammation; Intensive; Intensive care medicine; Laboratory animals; Laparotomy; Leukocyte migration; Leukocytes; Leukocytes - metabolism; Medical sciences; Medicine; Medicine & Public Health; Membrane permeability; Mice; Mice, Inbred C57BL; Microscopy; Microvasculature; Microvessels; Muscles; Nervous system; Pain Medicine; Pediatrics; Permeability; Peroxidase; Peroxidase - metabolism; Pneumology/Respiratory System; Rats; Rats, Wistar; Sepsis; Sepsis - metabolism; Sepsis - physiopathology; Sutures; Traffic; Brazil; Delirium; Sepsis; Brain microvasculature; Central nervous system; Intensive care; Leukocyte; Cytokine; Organic mental disorder; Encephalon; Infection; Sepsis syndrome; Mental confusion; Resuscitation
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-011-2151-2

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.