This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanni, L. A. Articles by Hunt, N. H. Search for Related Content PubMed PubMed Citation Articles by Sanni, L. A. Articles by Hunt, N. H.

(American Journal of Pathology. 2001;159:1105-1112.)
© 2001 American Society for Investigative Pathology

Regular Articles

Is Ischemia Involved in the Pathogenesis of Murine Cerebral Malaria?

Latifu A. Sanni^*, Caroline Rae, Annie Maitland^*, Roland Stocker and Nicholas H. Hunt^*

From the Departments of Pathology^*
and Biochemistry,
University of Sydney, Sydney; and the Biochemistry Group,
The Heart Research Institute, Camperdown, New South Wales, Australia

Sequestration of parasitized erythrocytes in the central nervous system microcirculation and increased cerebrospinal fluid lactate are prominent features of cerebral malaria (CM), suggesting that sequestration causes mechanical obstruction and ischemia. To examine the potential role of ischemia in the pathogenesis of CM, Plasmodium berghei ANKA (PbA) infection in CBA mice was compared to infection with P. berghei K173 (PbK) which does not cause CM (the non-CM model, NCM). Cerebral metabolite pools were measured by ¹H nuclear magnetic resonance spectroscopy during PbA and PbK infections. Lactate and alanine concentrations increased significantly at the terminal stage of CM, but not in NCM mice at any stage. These changes did not correlate with parasitemia. Brain NAD/NADH ratio was unchanged in CM and NCM mice at any time studied, but the total NAD pool size decreased significantly in the CM mice on day 7 after inoculation. Brain levels of glutamine and several essential amino acids were increased significantly in CM mice. There was a significant linear correlation between the time elapsed after infection and small, progressive decreases in the cell density/cell viability markers glycerophosphocholine and N-acetylaspartate in CM, indicative of gradual loss of cell viability. The metabolite changes followed a different pattern, with a sudden significant alteration in the levels of lactate, alanine, and glutamine at the time of terminal CM. In NCM, there were significant decreases with time of glutamate, the osmolyte myo-inositol, and glycerophosphocholine. These results are consistent with an ischemic change in the metabolic pattern of the brain in CM mice, whereas in NCM mice the changes were more consistent with hypoxia without vascular obstruction. Mild obstructive ischemia is a likely cause of the metabolic changes during CM, but a role for immune cell effector molecules cannot be ruled out.

This article has been cited by other articles:

				M.-F. Penet, A. Viola, S. Confort-Gouny, Y. Le Fur, G. Duhamel, F. Kober, D. Ibarrola, M. Izquierdo, N. Coltel, B. Gharib, et al. Imaging Experimental Cerebral Malaria In Vivo: Significant Role of Ischemic Brain Edema J. Neurosci., August 10, 2005; 25(32): 7352 - 7358. [Abstract] [Full Text] [PDF]

				C. RAE, J. A. MCQUILLAN, S. B. PAREKH, W. A. BUBB, S. WEISER, V. J. BALCAR, A. M. HANSEN, H. J. BALL, and N. H. HUNT Brain gene expression, metabolism, and bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria FASEB J, March 1, 2004; 18(3): 499 - 510. [Abstract] [Full Text] [PDF]