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Intravital Microscopy of the Mouse Brain Microcirculation using a Closed Cranial Window
Published on: November 18, 2010
Ultrastructural changes in the blood-brain barrier of mice infected with Plasmodium berghei
T W Polder1, W M Eling, J H Curfs
1Department of Neurosurgery, Catholic University of Nijmegen, The Netherlands.
Abstract:
Mice infected with the rodent malaria parasite Plasmodium berghei exhibit ultrastructural changes of the blood-brain barrier during the course of infection. Firm adherence including cellular interdigitation of infected cells or leucocytes and even clusters of cells to the vascular-endothelial lining is repeatedly observed early during infection. Ghosts and membrane remnants can be found engulfed in the surface of the endothelial cells. Frequently leucocytes migrate between endothelial cells and even cause a lift off and degeneration of these cells. In addition, endothelial cells exhibit increased pinocytotic activity, many irregular cytoplasmic extensions and even phagocytic activity. These changes are associated with degenerative changes in the basement membrane. Swelling and deposition of collagen-like fibres and even loss of fragments of basement membrane is observed. In some places fingerlike extensions of pericytes passed through the basement membrane and contacted or even bulged into the cytoplasm of endothelial cells. Ballooning and even coalescence of perivascular astrocytes was observed and contributed to the appearance of a perivascular oedematous space. The observed changes indicate a progressive deterioration of the blood-brain barrier eventually leading to endothelial lesions and hemorrhage.
Insights
Malaria parasite Plasmodium berghei infection damages the blood-brain barrier in mice. Ultrastructural changes reveal progressive deterioration, leading to potential hemorrhage.
Area of Science:
- Neuroscience
- Pathology
- Parasitology
Background:
- The blood-brain barrier (BBB) protects the central nervous system.
- Malaria infection can affect the brain, but BBB changes are not fully understood.
Purpose of the Study:
- To investigate the ultrastructural changes of the blood-brain barrier during Plasmodium berghei infection in mice.
Main Methods:
- Mice infected with Plasmodium berghei were examined using electron microscopy.
- Ultrastructural analysis focused on endothelial cells, basement membrane, pericytes, and astrocytes.
Main Results:
- Observed firm adherence of infected cells and leukocytes to the endothelium.
- Endothelial cells showed increased pinocytosis, cytoplasmic extensions, and phagocytosis.
- Degenerative changes in the basement membrane, pericyte extensions, and astrocyte swelling were noted.
- These alterations suggest a progressive BBB breakdown, leading to potential hemorrhage.
Conclusions:
- Plasmodium berghei infection causes significant ultrastructural damage to the blood-brain barrier.
- The observed changes indicate a progressive deterioration of BBB integrity.
- These findings contribute to understanding cerebral malaria pathogenesis and BBB dysfunction.
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