Electron microscopic features of brain edema in rodent cerebral malaria in relation to glial fibrillary acidic
Sumate Ampawong1, Urai Chaisri1, Parnpen Viriyavejakul1
1Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University 420/6, Ratchawithi Road, Ratchathewi, Bangkok, 10400, Thailand.
Abstract:
The mechanisms leading to cerebral malaria (CM) are not completely understood. Brain edema has been suggested as having an important role in experimental CM. In this study, CBA/CaH mice were infected with Plasmodium berghei ANKA blood-stage and when typical symptoms of CM developed on day 7, brain tissues were processed for electron-microscopic and immunohistochemical studies. The study demonstrated ultrastructural hallmarks of cerebral edema by perivascular edema and astroglial dilatation confirming existing evidence of vasogenic and cytogenic edema. This correlates closely with the clinical features of CM. An adaptive response of astrocytic activity, represented by increasing glial fibrillary acidic protein (GFAP) expression in the perivascular area and increasing numbers of large astrocyte clusters were predominately found in the CM mice. The presence of multivesicular and lamellar bodies indicates the severity of cerebral damage in experimental CM. Congestion of the microvessels with occluded white blood cells (WBCs), parasitized red blood cells (PRBCs) and platelets is also a crucial covariate role for CM pathogenesis.
Insights
Cerebral malaria (CM) involves brain edema, characterized by perivascular and astroglial changes. This study in mice reveals microvessel congestion and astrocyte activation, crucial factors in CM pathogenesis.
Area of Science:
- Neurology
- Immunology
- Pathology
Background:
- Cerebral malaria (CM) pathogenesis remains incompletely understood.
- Brain edema is a suspected key factor in experimental CM.
- Understanding CM mechanisms is vital for developing effective treatments.
Purpose of the Study:
- To investigate the ultrastructural and molecular changes in the brain during experimental CM.
- To correlate brain edema hallmarks with clinical CM symptoms.
- To elucidate the role of astrocytic activity and microvascular changes in CM.
Main Methods:
- CBA/CaH mice infected with Plasmodium berghei ANKA.
- Electron microscopy and immunohistochemical analysis of brain tissues on day 7 of infection.
- Assessment of perivascular edema, astroglial changes, GFAP expression, and microvessel congestion.
Main Results:
- Ultrastructural evidence of perivascular edema and astroglial dilatation (vasogenic and cytogenic edema) was observed.
- Increased glial fibrillary acidic protein (GFAP) expression and astrocyte clusters indicated adaptive astrocytic activity.
- Microvessel congestion with parasitized red blood cells, white blood cells, and platelets was identified as a critical factor.
Conclusions:
- Brain edema, characterized by specific ultrastructural changes, is a significant feature of experimental CM.
- Astrocytic activation and microvascular occlusion play crucial roles in CM pathogenesis.
- These findings provide insights into the complex mechanisms underlying cerebral malaria.
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