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

• Published in: European journal of pharmacology Vol. 697; no. 1-3; pp. 158 - 164
• Main Authors: Barichello, Tatiana, Ceretta, Renan A., Generoso, Jaqueline S., Moreira, Ana Paula, Simões, Lutiana R., Comim, Clarissa M., Quevedo, João, Vilela, Márcia Carvalho, Zuardi, Antonio Waldo, Crippa, José A., Teixeira, Antônio Lucio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2012
• Subjects: acute effects; adults; Animals; anti-inflammatory activity; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Arachnoid; Behavior, Animal - drug effects; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cannabidiol; Cannabidiol - administration & dosage; Cannabidiol - pharmacology; Chemokine; Chemokine CXCL1 - metabolism; Chemokines; cognition; Cognition - drug effects; Cognition Disorders - immunology; Cognition Disorders - microbiology; Cognition Disorders - physiopathology; Cognition Disorders - prevention & control; Cognition Disorders - psychology; Cognitive ability; complications (disease); cortex; Cortex (frontal); Cytokine; Cytokines; Disease Models, Animal; Down-Regulation; Frontal Lobe - drug effects; Frontal Lobe - immunology; Frontal Lobe - microbiology; Frontal Lobe - physiopathology; Hippocampus; Hippocampus - drug effects; Hippocampus - immunology; Hippocampus - microbiology; Hippocampus - physiopathology; Immune response; Infection; Inflammation; Inflammation Mediators - metabolism; Injections, Intraperitoneal; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; intraperitoneal injection; Learning; Male; Memory; Memory - drug effects; Meningitis; Meningitis, Pneumococcal - drug therapy; Meningitis, Pneumococcal - immunology; Meningitis, Pneumococcal - microbiology; Meningitis, Pneumococcal - physiopathology; Meningitis, Pneumococcal - psychology; Mortality; Neurological complications; Rats; Rats, Wistar; Seizures; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; subarachnoid space; Time Factors; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism; Chemokine; Meningitis; Cannabidiol; Memory; Cytokine; Streptococcus pneumoniae
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.09.053

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 10μl 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 10mg/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, 10mg/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.