| IJCEP Copyright © 2007-All rights reserved. |
Int J Clin Exp Pathol 2011;4(6):566-574
Original Ariticle
Quantitation of brain edema and localisation of aquaporin 4 expression in relation to
susceptibility to experimental cerebral malaria
Sumate Ampawong, Valéry Combes, Nicholas H Hunt, Jane Radford, Tailoi Chan-Ling, Emsri Pongponratn, Georges E R Grau
Vascular Immunology Unit, Dept. of Pathology, Faculty of Medicine and Bosch Institute, University of Sydney, Sydney, Australia; Department of
Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Molecular Immunopathology Unit, Dept. of Pathology,
Faculty of Medicine and Bosch Institute, University of Sydney, Sydney, Australia; Retinal & Developmental Neurobiology Lab, Dept. of Anatomy
and Histology, Faculty of Medicine and Bosch Institute, University of Sydney, Sydney, Australia.
Received June 14, 2011; accepted July 19, 2011; Epub July 23; published August 15, 2011
Abstract: The pathogenic mechanisms underlying the occurrence of cerebral malaria (CM) are still incompletely understood but, clearly,
cerebral complications may result from concomitant microvessel obstruction and inflammation. The extent to which brain edema contributes to
pathology has not been investigated. Using the model of P. berghei ANKA infection, we compared brain microvessel morphology of
CM-susceptible and CM-resistant mice. By quantitative planimetry, we provide evidence that CM is characterized by enlarged perivascular
spaces (PVS). We show a dramatic aquaporin 4 (AQP4) upregulation, selectively at the level of astrocytic foot processes, in both CM and
non-CM disease, but significantly more pronounced in mice with malarial-induced neurological syndrome. This suggests that a threshold of
AQP4 expression is needed to lead to neurovascular pathology, a view that is supported by significantly higher levels in mice with clinically overt
CM. Numbers of intravascular leukocytes significantly correlated with both PVS enlargement and AQP4 overexpression. Thus, brain edema
could be a contributing factor in CM pathogenesis and AQP4, specifically in its astrocytic location, a key molecule in this mechanism. Since
experimental CM is associated with substantial brain edema, it models paediatric CM better than the adult syndrome and it is tempting to
evaluate AQP4 in the former context. If AQP4 changes are confirmed in human CM, it may represent a novel target for therapeutic intervention.
(IJCEP1106004).
Keywords: Brain edema, aquaporin 4, astrocyte, endothelium, experimental cerebral malaria
Full text PDF
Address all correspondence to:
Georges E. R. Grau, MD,
PhD, Vascular Immunology Unit, Department of Pathology,
Faculty of Medicine and Bosch Institute, University
of Sydney, Sydney, Australia.
E-mail: georges.grau@sydney.edu.au;
Dr. Emsri Pongponratn,
Department of Tropical Pathology, Faculty of
Tropical Medicine, Mahidol University, Bangkok, Thailand.
E-mail: tmepp@mahidol.ac.th
Original Ariticle
Quantitation of brain edema and localisation of aquaporin 4 expression in relation to
susceptibility to experimental cerebral malaria
Sumate Ampawong, Valéry Combes, Nicholas H Hunt, Jane Radford, Tailoi Chan-Ling, Emsri Pongponratn, Georges E R Grau
Vascular Immunology Unit, Dept. of Pathology, Faculty of Medicine and Bosch Institute, University of Sydney, Sydney, Australia; Department of
Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Molecular Immunopathology Unit, Dept. of Pathology,
Faculty of Medicine and Bosch Institute, University of Sydney, Sydney, Australia; Retinal & Developmental Neurobiology Lab, Dept. of Anatomy
and Histology, Faculty of Medicine and Bosch Institute, University of Sydney, Sydney, Australia.
Received June 14, 2011; accepted July 19, 2011; Epub July 23; published August 15, 2011
Abstract: The pathogenic mechanisms underlying the occurrence of cerebral malaria (CM) are still incompletely understood but, clearly,
cerebral complications may result from concomitant microvessel obstruction and inflammation. The extent to which brain edema contributes to
pathology has not been investigated. Using the model of P. berghei ANKA infection, we compared brain microvessel morphology of
CM-susceptible and CM-resistant mice. By quantitative planimetry, we provide evidence that CM is characterized by enlarged perivascular
spaces (PVS). We show a dramatic aquaporin 4 (AQP4) upregulation, selectively at the level of astrocytic foot processes, in both CM and
non-CM disease, but significantly more pronounced in mice with malarial-induced neurological syndrome. This suggests that a threshold of
AQP4 expression is needed to lead to neurovascular pathology, a view that is supported by significantly higher levels in mice with clinically overt
CM. Numbers of intravascular leukocytes significantly correlated with both PVS enlargement and AQP4 overexpression. Thus, brain edema
could be a contributing factor in CM pathogenesis and AQP4, specifically in its astrocytic location, a key molecule in this mechanism. Since
experimental CM is associated with substantial brain edema, it models paediatric CM better than the adult syndrome and it is tempting to
evaluate AQP4 in the former context. If AQP4 changes are confirmed in human CM, it may represent a novel target for therapeutic intervention.
(IJCEP1106004).
Keywords: Brain edema, aquaporin 4, astrocyte, endothelium, experimental cerebral malaria
Full text PDF
Address all correspondence to:
Georges E. R. Grau, MD,
PhD, Vascular Immunology Unit, Department of Pathology,
Faculty of Medicine and Bosch Institute, University
of Sydney, Sydney, Australia.
E-mail: georges.grau@sydney.edu.au;
Dr. Emsri Pongponratn,
Department of Tropical Pathology, Faculty of
Tropical Medicine, Mahidol University, Bangkok, Thailand.
E-mail: tmepp@mahidol.ac.th
 | |  | |  | |  | |  | |  |
