Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis

^a Laboratório de Microbiologia Experimental e Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
^b Laboratório de Neurociências e Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
^c Departamento de Biologia Animal, Universidade Federal de Viçosa, Viçosa, MG, Brazil
^d Departamento de Neurociências e Ciências do comportamento da Faculdade de Medicina da Universidade de São Paulo e Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Ribeirão Preto, SP, Brazil
^e Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

http://dx.doi.org/10.1016/j.ejphar.2012.09.053, How to Cite or Link Using DOI

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Abstract

Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10 μl of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10 mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-α level in frontal cortex. Prolonged treatment with canabidiol, 10 mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel.

Keywords

Streptococcus pneumoniae;
Meningitis;
Cytokine;
Chemokine;
Memory;
Cannabidiol

Figures and tables from this article:

: Fig. 1. Kinetics of TNF-α levels in hippocampus and frontal cortex 6 h after meningitis induction by S. pneumoniae. The concentrations of TNF-α levels in hippocampus (A) and frontal cortex (B) were obtained 6 h after meningitis induction. Levels of cytokines/chemokine were assessed by ELISA and results are shown as pg of cytokine/chemokine per 100 mg of tissue. Results show the mean±S.E.M. of 5–6 animals in each group. Symbols indicate statistically significant when compared with sham group ^⁎P<0.05.; Figure options

: Fig. 2. Kinetics of IL-1β levels in hippocampus and frontal cortex 6 h after meningitis induction by S. pneumoniae. The concentrations of IL-1β levels in hippocampus (A) and frontal cortex (B) were obtained 6 h after meningitis induction. Levels of cytokines/chemokine were assessed by ELISA and results are shown as pg of cytokine/chemokine per 100 mg of tissue. Results show the mean±S.E.M. of 5–6 animals in each group. Symbols indicate statistically significant when compared with sham group ^⁎P<0.05.; Figure options

: Fig. 3. Kinetics of IL-6 levels in hippocampus and frontal cortex 6 h after meningitis induction by S. pneumoniae. The concentrations of IL-6 levels in hippocampus (A) and frontal cortex (B) were obtained 6 h after meningitis induction. Levels of cytokines/chemokine were assessed by ELISA and results are shown as pg of cytokine/chemokine per 100 mg of tissue. Results show the mean±S.E.M. of 5–6 animals in each group. Symbols indicate statistically significant when compared with sham group ^⁎P<0.05.; Figure options

: Fig. 4. Kinetics of CINC-1 levels in hippocampus and frontal cortex 6 h after meningitis induction by S. pneumoniae. The concentrations of CINC-1 levels in hippocampus (A) and frontal cortex (B) were obtained 6 h after meningitis induction. Levels of cytokines/chemokine were assessed by ELISA and results are shown as pg of cytokine/chemokine per 100 mg of tissue. Results show the mean±S.E.M. of 5–6 animals in each group. Symbols indicate statistically significant when compared with sham group ^⁎P<0.05.; Figure options

: Fig. 5. Kinetics of BDNF levels in hippocampus and frontal cortex 6 h after meningitis induction by S. pneumoniae. The concentrations of BDNF levels in hippocampus (A) and frontal cortex (B) were obtained 6 h after meningitis induction. Levels of BDNF were assessed by ELISA and results are shown as pg of BDNF per 100 mg of tissue. Results show the mean±S.E.M. of 5–6 animals in each group. ‘**’ Symbols indicate statistically significant when compared with sham group ^⁎⁎P<0.05.; Figure options

: Fig. 6. Kinetics of TNF-α levels in hippocampus and frontal cortex 10 days after meningitis induction by S. pneumoniae. The concentrations of TNF-α levels in hippocampus (A) and frontal cortex (B) were obtained 10 days after meningitis induction. Levels of cytokines/chemokine were assessed by ELISA and results are shown as pg of BDNF per 100 mg of tissue. Results show the mean±S.E.M. of 5–6 animals in each group. ‘*’ Symbol indicates statistically significant when compared with sham group ^⁎P<0.05. ‘**’ Symbols indicate statistically significant when compared with meningitis group without treatment ^⁎⁎P<0.05.; Figure options

: Fig. 7. Kinetics of BDNF levels in hippocampus and frontal cortex 10 days after meningitis induction by S. pneumoniae. The concentrations of BDNF levels in hippocampus (A) and frontal cortex (B) were obtained 10 days after meningitis induction. Levels of cytokines/chemokine were assessed by ELISA and results are shown as pg of BDNF per 100 mg of tissue. Results show the mean±S.E.M. of 5–6 animals in each group. ‘*’ Symbol indicates statistically significant when compared with sham group ^⁎P<0.05.; Figure options

: Fig. 8. Inhibitory avoidance test 10 days after induction of meningitis by S. pneumoniae. Data from the step-down inhibitory avoidance are presented as median and interquartile ranges, n=10 rats per group ^⁎P<0.05 versus training. Comparisons among groups were performed using Mann–Whitney U tests. Within individual groups it was analyzed by Wilcoxon test.; Figure options

: Corresponding author. Tel.: +55 48 99843615, +55 48 34312643; fax: +55 48 34434817.

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis.

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis

Abstract

Keywords

Freedom Wares

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