title: Inhibition of indoleamine 2,3-dioxygenase prevented cognitive impairment in adult Wistar rats subjected to pneumococcal meningitis.
abstract: Streptococcus pneumoniae is a common cause of forms of bacterial meningitis that have a high mortality rate and cause long-term neurologic sequelae. We evaluated the effects of an indoleamine 2,3-dioxygenase (IDO) inhibitor on proinflammatory mediators and memory in Wistar rats subjected to pneumococcal meningitis. The animals were divided into 4 groups: sham, sham treated with IDO inhibitor, meningitis, and meningitis treated with IDO inhibitor. During the first experiment, the animals were killed 24 hours later, and the hippocampus was isolated for the analysis of tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, and cytokine-induced neutrophil chemoattractant 1 (CINC-1) levels. The survival rate was 56.296% in the meningitis group and 29.616% in the meningitis group with IDO inhibitor. In the control group, we found a mean of 14.29 white blood cells/mL cerebrospinal fluid, whereas the mean was 80.00 white blood cells/mL cerebrospinal fluid in the sham IDO inhibitor group, 1167.00 white blood cells/mL cerebrospinal fluid in the meningitis group, and 286.70 white blood cells/mL cerebrospinal fluid in the meningitis IDO inhibitor group. In the meningitis group with IDO inhibitor, the levels of TNF-α and CINC-1 were reduced. In the second experiment, animals were subjected to a behavioral task and cytokine analysis 10 days after meningitis induction. In the meningitis group, there was an impairment of aversive memory. However, in the meningitis group that received adjuvant treatment with the IDO inhibitor, animals demonstrated preservation of aversive memory. These findings showed dual effects of the IDO inhibitor on a pneumococcal meningitis animal model because the inhibitor impaired survival but also produced beneficial effects, including anti-inflammatory activity and neuroprotection against the latter behavioral deficits.
authors.affiliation: Laboratório de Microbiologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil; Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil. Electronic address: tba@unesc.net.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: Generoso
authors.forename: Lutiana R
authors.initials: LR
authors.lastname: Simões
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Elias
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tashiro
authors.forename: Diogo
authors.initials: D
authors.lastname: Dominguini
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Comim
authors.forename: Márcia Carvalho
authors.initials: MC
authors.lastname: Vilela
authors.forename: Antonio Lucio
authors.initials: AL
authors.lastname: Teixeira
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D057170:Translational Research, Biomedical; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D014364:Tryptophan
keywords: CINC-1; CSF; IDO; IL; TNF; WBC; cerebral spinal fluid; cytokine-induced neutrophil chemoattractant 1; indoleamine 2,3-dioxygenase; interleukin; tumor necrosis factor; white blood cell