title: Lambda-carrageenan treatment exacerbates the severity of cerebral malaria caused by Plasmodium berghei ANKA in BALB/c mice.
abstract: BACKGROUND
  There is an urgent need to develop and test novel compounds against malaria infection. Carrageenans, sulphated polysaccharides derived from seaweeds, have been previously shown to inhibit Plasmodium falciparum in vitro. However, they are inflammatory and alter the permeability of the blood-brain barrier, raising concerns that their use as a treatment for malaria could lead to cerebral malaria (CM), a severe complication of the disease. In this work, the authors look into the effects of the administration of λ-carrageenan to the development and severity of CM in BALB/c mice, a relatively non-susceptible model, during infection with the ANKA strain of Plasmodium berghei.
  
  
  METHODS
  Five-week-old female BALB/c mice were infected with P. berghei intraperitoneally. One group was treated with λ-carrageenan (PbCGN) following the 4-day suppressive test protocol, whereas the other group was not treated (PbN). Another group of healthy BALB/c mice was similarly given λ-carrageenan (CGN) for comparison. The following parameters were assessed: parasitaemia, clinical signs of CM, and mortality. Brain and other vital organs were collected and examined for gross and histopathological lesions. Evans blue dye assays were employed to assess blood-brain barrier integrity.
  
  
  RESULTS
  Plasmodium berghei ANKA-infected BALB/c mice treated with λ-carrageenan died earlier than those that received no treatment. Histopathological examination revealed that intracerebral haemorrhages related to CM were present in both groups of infected BALB/c mice, but were more numerous in those treated with λ-carrageenan than in mock-treated animals. Inflammatory lesions were also observed only in the λ-carrageenan-treated mice. These observations are consistent with the clinical signs associated with CM, such as head tilt, convulsions, and coma, which were observed only in this group, and may account for the earlier death of the mice.
  
  
  CONCLUSIONS
  The results of this study indicate that the administration of λ-carrageenan exacerbates the severe brain lesions and clinical signs associated with CM in BALB/c mice infected with P. berghei ANKA.
authors.forename: Frances C
authors.initials: FC
authors.lastname: Recuenco
authors.forename: Ryo
authors.initials: R
authors.lastname: Takano
authors.forename: Shiori
authors.initials: S
authors.lastname: Chiba
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Sugi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takemae
authors.forename: Fumi
authors.initials: F
authors.lastname: Murakoshi
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishiwa
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inomata
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Horiuchi
authors.affiliation: Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. kkato@obihiro.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kato
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D002351:Carrageenan / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects*; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology*; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000175:diagnosis; D010962:Plasmodium berghei / Q000187:drug effects*; D016019:Survival Analysis
chemical_list: D000962:Antimalarials; D007155:Immunologic Factors; D002351:Carrageenan