title: Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria.
abstract: Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day-post-infection (dpi), at the peak of the disease), animals were treated with single or repeated doses of Artesunate, an antimalarial drug. All groups were tested for memory impairment (Novel Object Recognition or Morris Water Maze) and anxiety-like behaviors (Open field or elevated plus maze test) in different stages of the disease (at the peak or after the complete clearance of the disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and hippocampus of experimental groups. PbA-infected mice displayed memory deficits and exhibited increase in anxiety-like behaviors on the 5dpi or after the clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Infectious Diseases and Tropical Medicine Graduate Program, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil. Electronic address: allinecampos@usp.br.
authors.forename: A C
authors.initials: AC
authors.lastname: Campos
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Infectious Diseases and Tropical Medicine Graduate Program, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Brant
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Infectious Diseases and Tropical Medicine Graduate Program, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: A S
authors.initials: AS
authors.lastname: Miranda
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Infectious Diseases and Tropical Medicine Graduate Program, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: F S
authors.initials: FS
authors.lastname: Machado
authors.affiliation: Infectious Diseases and Tropical Medicine Graduate Program, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D037621:Artemisinins / Q000494:pharmacology; D000077332:Artesunate; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D008569:Memory Disorders / Q000188:drug therapy / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010962:Plasmodium berghei; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D002185:Cannabidiol; D000077332:Artesunate; D020932:Nerve Growth Factor
keywords: Cannabidiol; brain-derived neurotrophic factor; cerebral malaria; cytokines; inflammation