Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages
P. Lackner,
C. Burger, K. Pfaller,
V. Heussler,
R. Helbok, M. Morandell, G. Broessner, E. Tannich,
E. Schmutzhard, R. Beer,
Corresponding Author
P. Lackner
Department of Neurology and
Lackner Peter, Department of Neurology, Innsbruck Medical University, 6020 Innsbruck, Anichstrasse 35, Austria. Tel: +43 512 504 81011; Fax: +43 512 504 24243; E-mail: [email protected]Search for more papers by this authorK. Pfaller
Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria, and
Search for more papers by this authorV. Heussler
Department of Molecular Parasitology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
Search for more papers by this authorE. Tannich
Department of Molecular Parasitology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
Search for more papers by this authorP. Lackner,
C. Burger, K. Pfaller,
V. Heussler,
R. Helbok, M. Morandell, G. Broessner, E. Tannich,
E. Schmutzhard, R. Beer,
Corresponding Author
P. Lackner
Department of Neurology and
Lackner Peter, Department of Neurology, Innsbruck Medical University, 6020 Innsbruck, Anichstrasse 35, Austria. Tel: +43 512 504 81011; Fax: +43 512 504 24243; E-mail: [email protected]Search for more papers by this authorK. Pfaller
Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria, and
Search for more papers by this authorV. Heussler
Department of Molecular Parasitology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
Search for more papers by this authorE. Tannich
Department of Molecular Parasitology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
Search for more papers by this authorAbstract
Cerebral malaria (CM) is associated with high mortality and morbidity as a certain percentage of survivors suffers from persistent neurological sequelae. The mechanisms leading to death and functional impairments are yet not fully understood. This study investigated biochemical and morphological markers of apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved caspase-3 was detected in the brains of animals with clinical signs of CM and immunoreactivity directly correlated with the clinical severity of the disease. Caudal parts of the brain showed more intense immunoreactivity for cleaved caspase-3. Double-labelling experiments revealed processing of caspase-3 primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic-like morphological profiles in ultrastructural analysis. Further, cleavage of caspase-3 was found in endothelial cells. In contrast to neurons and oligodendrocytes, apoptosis of endothelial cells already occurred in early stages of the disease. Our results are the first to demonstrate processing of caspase-3 in different central nervous system cells of animals with CM. Apoptosis of endothelial cells may represent a critical issue for the development of the disease in the mouse model. Neurological signs and symptoms might be attributable, at least in part, to apoptotic degeneration of neurons and glia in advanced stages of murine CM.
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