Systemic and cerebral vascular endothelial growth factor levels increase in murine cerebral malaria along with increased calpain and caspase activity and can be reduced by erythropoietin treatment

Casper Hempel, Nils Hoyer, Anna Kildemoes, Charlotte Bille Jendresen, Jorgen Anders Lindholm Kurtzhals

Research output: Contribution to journalJournal articleResearchpeer-review

80 Downloads (Pure)

Abstract

The pathogenesis of cerebral malaria (CM) includes compromised microvascular perfusion, increased inflammation, cytoadhesion, and endothelial activation. These events cause blood brain barrier disruption and neuropathology and associations with the vascular endothelial growth factor (VEGF) signaling pathway have been shown. We studied this pathway in mice infected with Plasmodium berghei ANKA causing murine CM with or without the use of erythropoietin (EPO) as adjunct therapy. ELISA and western blotting was used for quantification of VEGF and relevant proteins in brain and plasma. CM increased levels of VEGF in brain and plasma and decreased plasma levels of soluble VEGF receptor 2. EPO treatment normalized VEGF receptor 2 levels and reduced brain VEGF levels. Hypoxia-inducible factor (HIF)-l alpha was significantly upregulated whereas cerebral HIF-2 alpha and EPO levels remained unchanged. Furthermore, we noticed increased caspase-3 and calpain activity in terminally ill mice, as measured by protease-specific cleavage of alpha-spectrin and p35. In conclusion, we detected increased cerebral and systemic VEGF as well as HI F-la, which in the brain were reduced to normal in EPO-treated mice. Also caspase and calpain activity was reduced markedly in EPO-treated mice.
Original languageEnglish
JournalFrontiers in Immunology
Volume5
Pages (from-to)291
Number of pages1
ISSN1664-3224
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Brain
  • Cerebral Malaria
  • Erythropoietin
  • Hypoxia
  • Inflammation
  • Neuropathology
  • VEGF

Fingerprint

Dive into the research topics of 'Systemic and cerebral vascular endothelial growth factor levels increase in murine cerebral malaria along with increased calpain and caspase activity and can be reduced by erythropoietin treatment'. Together they form a unique fingerprint.

Cite this