title: Sepsis-induced changes in behavioral stereotypy in rats; involvement of tumor necrosis factor-alpha, oxidative stress, and dopamine turnover.
abstract: BACKGROUND
  Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction that generally occurs early during severe sepsis. The complete pathophysiology of SAE is unknown, but several mechanisms including endotoxins, inflammatory mediators, the alteration of amino acids and of neurotransmitters, apoptosis, oxidative stress, and blood-brain barrier dysfunction have been suggested. The aim of the present study was to explore the relationship between behavioral stereotypy and plasma levels of tumor necrosis factor-alpha (TNF-α) and malondialdehyde (a marker of lipid peroxidation), and brain homovanillic acid content (a marker of dopamine turnover) in a surgically induced sepsis model in rats.
  
  
  METHODS
  Twenty-two adult male Sprague Dawley rats were included in the study. The cecal ligation and puncture procedure was performed to induce sepsis model. Apomorphine-induced stereotypy test was achieved 24 h after cecal ligation and puncture surgery and then, blood and brain samples were collected for biochemical measurements.
  
  
  RESULTS
  Significantly higher stereotypy score was found in sepsis group than in the sham group (P = 0.008). Furthermore, septic rats revealed significantly higher plasma TNF-α (P = 0.002) and malondialdehyde levels (P = 0.002), and brain homovanillic acid (P = 0.004) compared with sham rats. There was a significant and positive correlation between the behavioral and biochemical parameters.
  
  
  CONCLUSIONS
  Taken together, these results demonstrate the association between inflammatory response, oxidative stress, and stereotypic behavior in an experimental sepsis model. More comprehensive experimental and clinical studies are required to clarify the specific mechanisms underlying SAE.
authors.affiliation: Department of Physiology, Ege University School of Medicine, Izmir, Turkey.
authors.forename: Oytun
authors.initials: O
authors.lastname: Erbaş
authors.forename: Dilek
authors.initials: D
authors.lastname: Taşkıran
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000032:analysis; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000378:metabolism / Q000523:psychology*; D013239:Stereotyped Behavior; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D004298:Dopamine; D006719:Homovanillic Acid
keywords: Sepsis; TNF-α; homovanillic acid; oxidative stress; sepsis-associated encephalopathy; stereotypy