Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema.
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.
Penet
Marie-France
MF
Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6612, 13005 Marseille, France.
Viola
Angèle
A
Confort-Gouny
Sylviane
S
Le Fur
Yann
Y
Duhamel
Guillaume
G
Kober
Frank
F
Ibarrola
Danielle
D
Izquierdo
Marguerite
M
Coltel
Nicolas
N
Gharib
Bouchra
B
Grau
Georges E
GE
Cozzone
Patrick J
PJ
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology*; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology; D002560:Cerebrovascular Circulation; D005260:Female; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D016779:Malaria, Cerebral / Q000150:complications* / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology; D051379:Mice; D008808:Mice, Inbred CBA; D009474:Neurons / Q000473:pathology