Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA.
Malaria is a major cause of morbidity and mortality with an annual death toll exceeding one million. Severe malaria is a complex multisystem disorder, including one or more of the following complications: cerebral malaria, anemia, acidosis, jaundice, respiratory distress, renal insufficiency, coagulation anomalies, and hyperparasitemia. Using a combined in vivo/in vitro metabolic-based approach, we investigated the putative pathogenic effects of Plasmodium berghei ANKA on brain, in a mouse strain developing malaria but resistant to cerebral malaria. The purpose was to determine whether the infection could cause a brain dysfunction distinct from the classic cerebral syndrome. Mice resistant to cerebral malaria were infected with P. berghei ANKA and explored during both the symptomless and the severe stage of the disease by using in vivo brain magnetic resonance imaging and spectroscopy. The infected mice did not present the lesional and metabolic hallmarks of cerebral malaria. However, brain dysfunction caused by anemia, parasite burden, and hepatic damage was evidenced. We report an increase in cerebral blood flow, a process allowing temporary maintenance of oxygen supply to brain despite anemia. Besides, we document metabolic anomalies affecting choline-derived compounds, myo-inositol, glutamine, glycine, and alanine. The choline decrease appears related to parasite proliferation. Glutamine, myo-inositol, glycine, and alanine variations together indicate a hepatic encephalopathy, a finding in agreement with the liver damage detected in mice, which is also a feature of the human disease. These results reveal the vulnerability of brain to malaria infection at the severe stage of the disease even in the absence of cerebral malaria.
Penet
Marie-France
MF
Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche (UMR) CNRS 6612, Facultéde Médecine la Timone, UniversitédelaMéditerranée, Marseille, France.
Kober
Frank
F
Confort-Gouny
Sylviane
S
Le Fur
Yann
Y
Dalmasso
Christiane
C
Coltel
Nicolas
N
Liprandi
Agnès
A
Gulian
Jean-Marc
JM
Grau
Georges E
GE
Cozzone
Patrick J
PJ
Viola
Angèle
A
D000409:Alanine; D000740:Anemia / Q000209:etiology / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology; D049109:Cell Proliferation; D002560:Cerebrovascular Circulation; D005260:Female; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D016779:Malaria, Cerebral / Q000150:complications / Q000175:diagnosis*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000472:pathogenicity*
D000409:Alanine