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Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO.

Karlsson, Michael LU ; Hempel, Casper; Sjövall, Fredrik LU ; Hansson, Magnus LU ; Kurtzhals, Jørgen A L and Elmer, Eskil LU (2013) In International Journal of Biochemistry and Cell Biology 45(1). p.5-151
Abstract
Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection. The pathogenesis of CM is complex. Cerebral metabolic dysfunction is implicated in CM, which may be caused by both an impaired cerebral microcirculation and a dysregulated inflammatory response affecting cellular respiration of mitochondria. Recombinant human erythropoietin (rhEPO) is a promising new therapy that has been shown to reduce mortality in a mouse model of CM. In order to further elucidate the metabolic dysfunction in CM the objective of the present study was to assess brain mitochondrial respiratory function in CM with and without rhEPO treatment. The P. berghei ANKA - C57BL/6 murine model of CM was used. Mitochondrial respiration was... (More)
Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection. The pathogenesis of CM is complex. Cerebral metabolic dysfunction is implicated in CM, which may be caused by both an impaired cerebral microcirculation and a dysregulated inflammatory response affecting cellular respiration of mitochondria. Recombinant human erythropoietin (rhEPO) is a promising new therapy that has been shown to reduce mortality in a mouse model of CM. In order to further elucidate the metabolic dysfunction in CM the objective of the present study was to assess brain mitochondrial respiratory function in CM with and without rhEPO treatment. The P. berghei ANKA - C57BL/6 murine model of CM was used. Mitochondrial respiration was analyzed in brain homogenates using high-resolution respirometry and a multiple substrate and inhibitor protocol. The animals were divided into four groups; infected injected with saline or with rhEPO, non-infected injected with saline or with rhEPO. Infected mice developed CM and treatment with rhEPO attenuated clinical signs of disease. There were no differences in respiratory parameters of brain mitochondria between infected and non-infected mice and no connection between disease severity and mitochondrial respiratory function. Treatment with rhEPO similarly had no effect on respiratory function. Thus cerebral metabolic dysfunction in CM does not seem to be directly linked to altered mitochondrial respiratory capacity as analyzed in brain homogenates ex vivo. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
International Journal of Biochemistry and Cell Biology
volume
45
issue
1
pages
5 - 151
publisher
Elsevier
external identifiers
  • wos:000314073400022
  • pmid:22903021
  • scopus:84870654878
ISSN
1878-5875
DOI
10.1016/j.biocel.2012.08.008
language
English
LU publication?
yes
id
ef0b0b7a-ea6b-4d80-9566-fbe28815fa2d (old id 3047384)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22903021?dopt=Abstract
date added to LUP
2012-09-05 20:06:11
date last changed
2017-03-26 04:31:21
@article{ef0b0b7a-ea6b-4d80-9566-fbe28815fa2d,
  abstract     = {Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection. The pathogenesis of CM is complex. Cerebral metabolic dysfunction is implicated in CM, which may be caused by both an impaired cerebral microcirculation and a dysregulated inflammatory response affecting cellular respiration of mitochondria. Recombinant human erythropoietin (rhEPO) is a promising new therapy that has been shown to reduce mortality in a mouse model of CM. In order to further elucidate the metabolic dysfunction in CM the objective of the present study was to assess brain mitochondrial respiratory function in CM with and without rhEPO treatment. The P. berghei ANKA - C57BL/6 murine model of CM was used. Mitochondrial respiration was analyzed in brain homogenates using high-resolution respirometry and a multiple substrate and inhibitor protocol. The animals were divided into four groups; infected injected with saline or with rhEPO, non-infected injected with saline or with rhEPO. Infected mice developed CM and treatment with rhEPO attenuated clinical signs of disease. There were no differences in respiratory parameters of brain mitochondria between infected and non-infected mice and no connection between disease severity and mitochondrial respiratory function. Treatment with rhEPO similarly had no effect on respiratory function. Thus cerebral metabolic dysfunction in CM does not seem to be directly linked to altered mitochondrial respiratory capacity as analyzed in brain homogenates ex vivo. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.},
  author       = {Karlsson, Michael and Hempel, Casper and Sjövall, Fredrik and Hansson, Magnus and Kurtzhals, Jørgen A L and Elmer, Eskil},
  issn         = {1878-5875},
  language     = {eng},
  number       = {1},
  pages        = {5--151},
  publisher    = {Elsevier},
  series       = {International Journal of Biochemistry and Cell Biology},
  title        = {Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO.},
  url          = {http://dx.doi.org/10.1016/j.biocel.2012.08.008},
  volume       = {45},
  year         = {2013},
}