Imaging experimental cerebral malaria in vivo: Significant role of ischemic brain edema

Marie France Penet, Angèle Viola, Sylviane Confort-Gouny, Yann Le Fur, Guillaume Duhamel, Frank Kober, Danielle Ibarrola, Marguerite Izquierdo, Nicolas Coltel, Bouchra Gharib, Georges E. Grau, Patrick J. Cozzone

Research output: Contribution to journalArticlepeer-review

Abstract

The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood- brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemie lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

Original languageEnglish (US)
Pages (from-to)7352-7358
Number of pages7
JournalJournal of Neuroscience
Volume25
Issue number32
DOIs
StatePublished - Aug 10 2005

Keywords

  • Edema
  • Experimental cerebral malaria
  • Ischemia
  • Metabolism
  • Mice
  • Neuroimaging

ASJC Scopus subject areas

  • Neuroscience(all)

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