PMID- 25595981
OWN - NLM
STAT- MEDLINE
DCOM- 20151125
LR  - 20181202
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 289
DP  - 2015 Mar 19
TI  - Cannabidiol increases survival and promotes rescue of cognitive function in a 
      murine model of cerebral malaria.
PG  - 166-80
LID - S0306-4522(15)00019-6 [pii]
LID - 10.1016/j.neuroscience.2014.12.051 [doi]
AB  - 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-alpha 
      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-alpha) 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.
CI  - Copyright (c) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Campos, A C
AU  - Campos AC
AD  - 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.
FAU - Brant, F
AU  - Brant F
AD  - 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.
FAU - Miranda, A S
AU  - Miranda AS
AD  - 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.
FAU - Machado, F S
AU  - Machado FS
AD  - 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.
FAU - Teixeira, A L
AU  - Teixeira AL
AD  - Infectious Diseases and Tropical Medicine Graduate Program, School of Medicine, 
      Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150113
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 19GBJ60SN5 (Cannabidiol)
RN  - 60W3249T9M (Artesunate)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Antimalarials/*pharmacology
MH  - Anxiety/drug therapy/physiopathology
MH  - Artemisinins/pharmacology
MH  - Artesunate
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cannabidiol/*pharmacology
MH  - Cognition/*drug effects/physiology
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Female
MH  - Hippocampus/drug effects/physiopathology
MH  - Malaria, Cerebral/*drug therapy/physiopathology/psychology
MH  - Memory Disorders/drug therapy/physiopathology
MH  - Mice, Inbred C57BL
MH  - Nerve Growth Factor/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - *Plasmodium berghei
MH  - Prefrontal Cortex/drug effects/physiopathology
MH  - Survival Analysis
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Cannabidiol
OT  - brain-derived neurotrophic factor
OT  - cerebral malaria
OT  - cytokines
OT  - inflammation
EDAT- 2015/01/18 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/01/18 06:00
PHST- 2014/08/19 00:00 [received]
PHST- 2014/12/26 00:00 [revised]
PHST- 2014/12/31 00:00 [accepted]
PHST- 2015/01/18 06:00 [entrez]
PHST- 2015/01/18 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0306-4522(15)00019-6 [pii]
AID - 10.1016/j.neuroscience.2014.12.051 [doi]
PST - ppublish
SO  - Neuroscience. 2015 Mar 19;289:166-80. doi: 10.1016/j.neuroscience.2014.12.051. 
      Epub 2015 Jan 13.