title: Antioxidant treatment prevents cognitive impairment and oxidative damage in pneumococcal meningitis survivor rats.
abstract: Pneumococcal meningitis is associated with the highest fatality case ratios in the world. Most of patients that survive present neurologic sequelae at later times as well as biochemicals alterations such as oxidative stress in both earlier and later times after central nervous system infection. In this context, we evaluated the effect of antioxidant treatment on memory and oxidative parameters in the hippocampus of meningitis survivor rats 10 days after infection. To this aim, the animals underwent a magna cistern tap receiving either 10 μL sterile saline as a placebo or an equivalent volume of a Streptococcus pneumoniae suspension at the concentration 5x10(9) cfu/mL. The animals submitted to meningitis were divided into the following groups: 1) treated with antibiotic, 2) treated with basic support plus N-acetylcysteine, 3) treated with basic support plus deferoxamine, 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. Ten days after meningitis, the animals underwent inhibitory avoidance and habituation to an open field tasks and, immediately after, were assessed for oxidative damage in the hippocampus and cortex. The meningitis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the meningitis group presented memory impairment after meningitis. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine with or without basic support and its isolate use. In addition, there was an increase of lipid phosphorylation in cortex and hippocampus and all the combined antioxidants attenuated lipid phosphorylation in both structures. On the other hand, there was an increase of protein phosphorylation in cortex and N-acetylcysteine plus deferoxamine with or without basic support prevented it. Thus, we hypothesize that oxidative stress may be related to cognitive impairment in pneumococcal meningitis.
authors.affiliation: Laboratory of Experimental Microbiology and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000, Criciúma, SC, Brazil. tba@unesc.net
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Ana Lucia B
authors.initials: AL
authors.lastname: Santos
authors.forename: Geovana D
authors.initials: GD
authors.lastname: Savi
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: Generoso
authors.forename: Paola
authors.initials: P
authors.lastname: Otaran
authors.forename: Cleonice M
authors.initials: CM
authors.lastname: Michelon
authors.forename: Amanda V
authors.initials: AV
authors.lastname: Steckert
authors.forename: Francielle
authors.initials: F
authors.lastname: Mina
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Comim
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000517:prevention & control*; D003676:Deferoxamine / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000523:psychology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017741:Survivors; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; D003676:Deferoxamine; D000111:Acetylcysteine