Reduced cerebral blood flow and N-acetyl aspartate in a murine model of cerebral malaria.
Cerebral malaria is an important cause of morbidity and mortality in many parts of the world. It has been suggested that cerebral malaria is associated with reduced perfusion due to the blockage of blood vessels by parasitized erythrocytes; although, no quantitative validation of this has been done. We infected C57BL/6 mice with the ANKA strain of Plasmodium berghei and on day 6 of infection we investigated alterations in brain function using arterial spin labeling MRI and proton MRS. MR images did not demonstrate signs of damage. However, there was a significant reduction in cerebral blood flow (P<0.012) and the ratio of N-acetyl-aspartate (NAA) to creatine (Cr) (P<0.01) relative to non-infected mice. The NAA/Cr ratios were significantly correlated with cerebral perfusion (r=0.87) suggesting a relationship between impaired oxygen delivery and neuronal dysfunction. Pathological examination revealed accumulations of damaged axons providing a correlate for the decreased NAA/Cr ratio in infected mice. This murine model will permit non-invasive studies of neurologic function during malarial infection.
Kennan
Richard P
RP
Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Machado
Fabiana S
FS
Lee
Sunhee C
SC
Desruisseaux
Mahalia S
MS
Wittner
Murray
M
Tsuji
Moriya
M
Tanowitz
Herbert B
HB
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001369:Axons / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D015536:Down-Regulation; D008279:Magnetic Resonance Imaging; D016779:Malaria, Cerebral / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei; D011859:Radiography
D001224:Aspartic Acid; C000179:N-acetylaspartate