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Updated: Aug 30, 2026
In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging
Published on: June 8, 2017
Angiogenic proteins in brains of patients who died with cerebral malaria
Martin H Deininger1, Stefan Winkler, Peter G Kremsner
1Institute of Brain Research, University of Tuebingen, Medical School, Calwer Str. 3, D-72076 Tübingen, Germany. martin.deininger@uni-tuebingen.de
Abstract:
In cerebral malaria (CM), microvascular activation accompanies blood-brain barrier dysfunction which in turn represents the pathophysiological basis of neurological impairments in affected patients. To dissect the molecular basis of this process, we analyzed localization of proangiogenic vascular endothelial growth factor (VEGF), its receptor vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1), of downstream VEGF effectors matrix-metalloproteinase-1 (MMP-1) and connective tissue growth factor (CTGF), and of VEGF-interacting antiangiogenic thrombospondin-1 and -independent angiostatin in brains of patients who died with CM and controls by immunohistochemistry and Western blotting experiments. Most prominently, we detected more VEGF(+) astrocytes in CM patients and deposition of Flt-1 in Dürck's granulomas. MMP-1 and thrombospondin-1 accumulated in macrophages/microglial cells in Dürck's granulomas. In one CM patient, massive amounts of CTGF were detected as perivascular paracellular deposits. Angiostatin was observed in the serum of 2/7 control but in no CM patients. These data demonstrate the activation of the proangiogenic VEGF signaling cascade in patients with CM, probably reflecting compensatory mechanisms of general and focal brain hypoxia observed in these patients.
Insights
Cerebral malaria (CM) involves brain blood vessel changes. Researchers found the proangiogenic vascular endothelial growth factor (VEGF) signaling pathway is activated in CM brains, possibly due to hypoxia.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Cerebral malaria (CM) is characterized by microvascular activation and blood-brain barrier dysfunction, leading to neurological impairments.
- The molecular mechanisms underlying these changes in CM are not fully understood.
Purpose of the Study:
- To investigate the role of vascular endothelial growth factor (VEGF) signaling in the brains of patients with cerebral malaria.
- To analyze the expression and localization of key components of the VEGF pathway and related molecules.
Main Methods:
- Immunohistochemistry and Western blotting were used to examine brain tissue from CM patients and controls.
- Analysis focused on VEGF, its receptor VEGFR-1 (Flt-1), downstream effectors (MMP-1, CTGF), and antiangiogenic factors (thrombospondin-1, angiostatin).
Main Results:
- Increased VEGF-positive astrocytes were observed in CM brains.
- Flt-1 deposition occurred in Dürck's granulomas, and MMP-1 and thrombospondin-1 accumulated in macrophages/microglial cells within these lesions.
- Massive CTGF deposits were found perivascularly in one CM patient; angiostatin was absent in CM patients but present in some controls.
Conclusions:
- The proangiogenic VEGF signaling cascade is activated in cerebral malaria.
- This activation may represent a compensatory response to general and focal brain hypoxia in CM patients.
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