TY - JOUR
T1 - Imaging experimental cerebral malaria in vivo
T2 - Significant role of ischemic brain edema
AU - Penet, Marie France
AU - Viola, Angèle
AU - Confort-Gouny, Sylviane
AU - Le Fur, Yann
AU - Duhamel, Guillaume
AU - Kober, Frank
AU - Ibarrola, Danielle
AU - Izquierdo, Marguerite
AU - Coltel, Nicolas
AU - Gharib, Bouchra
AU - Grau, Georges E.
AU - Cozzone, Patrick J.
PY - 2005/8/10
Y1 - 2005/8/10
N2 - 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.
AB - 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.
KW - Edema
KW - Experimental cerebral malaria
KW - Ischemia
KW - Metabolism
KW - Mice
KW - Neuroimaging
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U2 - 10.1523/JNEUROSCI.1002-05.2005
DO - 10.1523/JNEUROSCI.1002-05.2005
M3 - Article
C2 - 16093385
AN - SCOPUS:23744506305
SN - 0270-6474
VL - 25
SP - 7352
EP - 7358
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 32
ER -