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The Journal of Neuroscience, August 10, 2005, 25(32):7352-7358; doi:10.1523/JNEUROSCI.1002-05.2005

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Neurobiology of Disease
Imaging Experimental Cerebral Malaria In Vivo: Significant Role of Ischemic Brain Edema

Marie-France Penet,1,2 * Angèle Viola,1 * Sylviane Confort-Gouny,1 Yann Le Fur,1 Guillaume Duhamel,1 Frank Kober,1 Danielle Ibarrola,1 Marguerite Izquierdo,1 Nicolas Coltel,3 Bouchra Gharib,2 Georges E. Grau,3 and Patrick J. Cozzone1

1Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique (UMR CNRS) 6612, 2Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale U399, and 3Unité des Rickettsies et des Pathogènes Emergents, UMR CNRS 6020, Institut Fédératif de Recherche 48, UniversitédelaMéditerranée, 13005 Marseille, France

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 ischemic 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.

Key words: neuroimaging; ischemia; edema; experimental cerebral malaria; metabolism; mice

Received March 15, 2005; revised May 2, 2005; accepted June 30, 2005.




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