title: alpha-Tocopherol transfer protein inhibition is effective in the prevention of cerebral malaria in mice.
abstract: BACKGROUND
  Nutritional status likely plays an important role in determining the outcome of protozoan infections. Despite the evidence of Plasmodium sensitivity to oxidative stress, the potential role of vitamin E, a free radical scavenger, on the outcome of cerebral malaria (CM) has yet to be elucidated.
  
  
  OBJECTIVE
  To determine the influence of vitamin E on Plasmodium parasite development and murine CM outcome, alpha-tocopherol transfer protein (alpha-TTP), a regulator of vitamin E in the host circulation, was abrogated.
  
  
  METHODS
  alpha-TTP knockout mice were infected with Plasmodium berghei ANKA, and survival rate, parasitemia, brain histologic alterations, and brain barrier permeability were assessed. In addition, mRNA expression of the cytokines and adhesion molecules involved in this neurologic pathology were monitored.
  
  
  RESULTS
  alpha-TTP knockout mice infected with P. berghei ANKA did not exhibit any clinical or pathologic signs of CM, and a histologic analysis of the brain tissues in these animals showed no alteration of blood-brain barrier integrity compared with that in control mice. Interestingly, protection of the blood-brain barrier in these infected alpha-TTP knockout mice was lost when dietary supplementation with vitamin E was added to their diet. Moreover, interleukins and adhesion molecule transcripts in the brain of control mice were significantly up-regulated compared with those in the alpha-TTP knockout mice.
  
  
  CONCLUSIONS
  It appears that a deficiency of alpha-tocopherol in the circulation prevents CM and suggests that alpha-TTP is a putative target for the early prevention of CM.
authors.affiliation: Research Unit for Functional Genomics, National Research Center for Protozoan Diseases, Obihiro University of Agriculture, Tokyo, Japan.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Herbas
authors.forename: Mikiko
authors.initials: M
authors.lastname: Okazaki
authors.forename: Eri
authors.initials: E
authors.lastname: Terao
authors.forename: Xuenan
authors.initials: X
authors.lastname: Xuan
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D016779:Malaria, Cerebral / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D010961:Plasmodium; D010962:Plasmodium berghei; D012333:RNA, Messenger / Q000235:genetics; D014801:Vitamin A / Q000097:blood; D014802:Vitamin A Deficiency / Q000235:genetics*; D014810:Vitamin E / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D012333:RNA, Messenger; C017763:alpha-tocopherol transfer protein; D014801:Vitamin A; D014810:Vitamin E