| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Pathology*
and Anatomy
and Histology,
Institute for Biomedical
Research, University of Sydney, Sydney, New South Wales, Australia.
Microglial activation and redistribution toward blood vessels are
some of the earliest observable events occurring within the central
nervous system (CNS) during fatal murine cerebral malaria (FMCM). To
investigate stimuli that might modulate microglial reactivity during
FMCM we have performed two experimental manipulations and observed
microglial responses in retinal whole mounts. First, to
determine whether increased blood-brain barrier (BBB) permeability in
the absence of the malaria parasite initiates the microglial
changes, BBB function was compromised experimentally by
intracarotid injection of arabinose and retinae were examined
12, 24, or 36 hours later. Second, to determine
whether the immune response against the malaria parasite modulates
microglial reactivity, infected mice were treated with
dexamethasone before day 4 postinoculation. This treatment regime
ameliorates cerebral complications without affecting parasite growth.
We observed that increased BBB permeability was sufficient to elicit
thickening of microglial processes and redistribution of microglia
toward the vasculature, characteristic of the early stages of
FMCM. However, despite the presence of plasma constituents in
the CNS for up to 36 hours, microglia with amoeboid and
vacuolated morphology were not observed. Dexamethasone treatment
inhibited the up-regulation of 
-D-galactose expression and reactive
morphological changes in microglia during FMCM. These results suggest
that disruption of the CNS milieu by entry of plasma
constituents, or circulating malaria parasites in the absence
of an immune response, by themselves are insufficient to induce
the reactive microglial changes that are characteristic of FMCM. In
addition, dexamethasone-sensitive event(s), presumably
associated with immune system activation, occurring within the
first few days of malaria infection are essential for the development
of reactive microglia and subsequent fatal neurological
complications.
This article has been cited by other articles:
 |
|
 |
|
  J. Miu, N. H. Hunt, and H. J. Ball Predominance of Interferon-Related Responses in the Brain during Murine Malaria, as Identified by Microarray Analysis Infect. Immun., May 1, 2008; 76(5): 1812 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Rock, G. Gekker, S. Hu, W. S. Sheng, M. Cheeran, J. R. Lokensgard, and P. K. Peterson Role of Microglia in Central Nervous System Infections Clin. Microbiol. Rev., October 1, 2004; 17(4): 942 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Baetas-da-Cruz, R. M. Macedo-Silva, A. Santos-Silva, A. Henriques-Pons, M. F. Madeira, S. Corte-Real, and L. A. Cavalcante Destiny and Intracellular Survival of Leishmania amazonensis in Control and Dexamethasone-treated Glial Cultures: Protozoa-specific Glycoconjugate Tagging and TUNEL Staining J. Histochem. Cytochem., August 1, 2004; 52(8): 1047 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. van der Heyde, P. Bauer, G. Sun, W.-L. Chang, L. Yin, J. Fuseler, and D. N. Granger Assessing Vascular Permeability during Experimental Cerebral Malaria by a Radiolabeled Monoclonal Antibody Technique Infect. Immun., May 1, 2001; 69(5): 3460 - 3465. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
