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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
Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema
Marie-France Penet1, Angèle Viola, Sylviane Confort-Gouny
1Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6612, 13005 Marseille, France.
Abstract:
The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.
Insights
This study reveals how cerebral malaria causes brain swelling and blood flow collapse in mice. These findings offer new insights into malaria
Area of Science:
- Neuroscience
- Immunology
- Medical Imaging
Background:
- Cerebral malaria is a lethal complication of malaria.
- Understanding its pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the in vivo brain changes associated with experimental cerebral malaria using multimodal magnetic resonance techniques.
- To elucidate the mechanisms leading to the fatal outcome in cerebral malaria.
Main Methods:
- Utilized in vivo magnetic resonance imaging (MRI), diffusion, perfusion, angiography, and spectroscopy in mice infected with Plasmodium berghei ANKA.
- Applied a multimodal approach to assess vascular integrity, edema, perfusion, and metabolic changes in the brain.
Main Results:
- Demonstrated blood-brain barrier disruption and hemorrhages, indicative of inflammatory vascular damage.
- Detected significant edema formation and reduced brain perfusion, leading to an ischemic metabolic profile (decreased high-energy phosphates, increased lactate).
- Angiography revealed hemodynamic dysfunction, with edema exacerbating ischemia by compressing cerebral arteries and causing blood flow collapse.
Conclusions:
- Edema plays a critical role in the fatal outcome of experimental cerebral malaria by worsening ischemia.
- Findings highlight the coexistence of inflammatory and ischemic lesions in cerebral malaria.
- The study provides potential noninvasive surrogate markers for monitoring treatment efficacy in cerebral malaria.
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