Quantitation of brain edema and localisation of aquaporin 4 expression in relation to susceptibility to experimental cerebral malaria

Ampawong, S; Combes, V; Hunt, NH; Radford, J; Chan-Ling, T; Pongponratn, E; Grau, GER

Quantitation of brain edema and localisation of aquaporin 4 expression in relation to susceptibility to experimental cerebral malaria

Ampawong, S Combes, V

Hunt, NH Radford, J Chan-Ling, T Pongponratn, E Grau, GER

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Publication Type:: Journal Article
Citation:: International Journal of Clinical and Experimental Pathology, 2011, 4 (6), pp. 566 - 574
Issue Date:: 2011-11-02

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Field	Value	Language
dc.contributor.author	Ampawong, S	en_US
dc.contributor.author	Combes, V https://orcid.org/0000-0003-2178-3596	en_US
dc.contributor.author	Hunt, NH	en_US
dc.contributor.author	Radford, J	en_US
dc.contributor.author	Chan-Ling, T	en_US
dc.contributor.author	Pongponratn, E	en_US
dc.contributor.author	Grau, GER	en_US
dc.date.available	2011-07-19	en_US
dc.date.issued	2011-11-02	en_US
dc.identifier.citation	International Journal of Clinical and Experimental Pathology, 2011, 4 (6), pp. 566 - 574	en_US
dc.identifier.uri	http://hdl.handle.net/10453/109926
dc.description.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.	en_US
dc.relation.ispartof	International Journal of Clinical and Experimental Pathology	en_US
dc.subject.classification	Oncology & Carcinogenesis	en_US
dc.subject.mesh	Brain	en_US
dc.subject.mesh	Astrocytes	en_US
dc.subject.mesh	Leukocytes	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Inbred CBA	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Plasmodium berghei	en_US
dc.subject.mesh	Malaria, Cerebral	en_US
dc.subject.mesh	Brain Edema	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Biological Markers	en_US
dc.subject.mesh	Species Specificity	en_US
dc.subject.mesh	Up-Regulation	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Aquaporin 4	en_US
dc.subject.mesh	Biomarkers	en_US
dc.title	Quantitation of brain edema and localisation of aquaporin 4 expression in relation to susceptibility to experimental cerebral malaria	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.citation.volume	4	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	4	en_US

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/109926