Name: in vivo tracking of edema development and microvascular pathology in a model of experimental cerebral malaria using magnetic resonance imaging
Uploaded: 2017-06-08T12:30:00
Description: Watch this Scientific Journal Video about In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging at JoVE.com

The expert technical assistance of Miriam Reinig is gratefully acknowledged. AH received funding from a postdoctoral stipend of the Medical Faculty of the University of Heidelberg. MP is supported by a memorial stipend from the Else-Kro&#776;ner-Fresenius Foundation. AKM is a recipient of a maternity leave stipend by the DZIF Academy of the German Center for Infection Research (DZIF). JP is the recipient of a Heidelberg Research Center for Molecular Medicine (HRCMM) Career Development Fellowship. We furthermore gratefully acknowledge Julia M. Sattler and Friedrich Frischknecht for providing an exemplary movie of sporozoite movement.

All animal experiments reported in this article were conducted according to the Federation for Laboratory Animal Science Associations (FELASA) category B and the Society of Laboratory Animal Science (GV-SOLAS) standard guidelines and were approved by the local German authorities in Karlsruhe (Regierungspr&#228;sidium Karlsruhe, Germany). Please note that biosavety level 2 applies to mosquito and Plasmodium berghei ANKA sporozoite work.
1. Infection
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	<li>Infect Anopheles stephensi</e...

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In this article, we describe a whole-brain MRI protocol to delineate changes in experimental cerebral malaria. We believe that MRI has been under-utilized in malaria research to date and hope that our protocols will aid other investigators. We would like to describe some additional points that may be helpful.
If severely sick mice are imaged, positioning is crucial. Due to increased intracranial pressure, mice are susceptible to death, and thus, the cervical spine should not be stretched. Anes...

Malaria is a significant global health problem.1 Severe malaria is characterized in part by cerebral involvement and is often a poor prognostic factor. Cerebral involvement is common in children under the age of five in areas of high malaria transmission and represents the major cause of malaria related death in that age group.1 While aggressive treatment can be life-saving, the detection of cerebral malaria, especially in early stages, can be difficult. The pathological processes involved in cerebral malaria include microvascular disruption and cerebral edema, which can lead to severe brain swelling. In this article, we present a magnetic resonance imaging (MRI) protocol that allows whole-brain in vivo imaging of experimental cerebral malaria (ECM). Whole-brain high-resolution imaging methods have been widely underutilized in this disease, even though little is known about how ECM initiates in the central nervous system or what specific mechanisms lead to the disease. In vivo MRI, covering the whole brain, represents an important research tool to gain a better understanding of ECM pathology. MRI is able to assess global cerebral brain swelling, which has recently been recognized to be an important predictor of death not only in ECM, but also in human cerebral malaria.2,3 Severe brain swelling occurs in fatal disease and represents one of several pathological features between the ECM models and human disease, a disease that is characterized by both inflammatory and microvascular alterations.4
ECM can be induced in CBA or C57BL mice through infection with lethal Plasmodium berghei ANKA.5 The onset of ECM typically occurs between days 6 and 10 post-infection and results in fitting, ataxia, respiratory distress, and coma, which lead to rapid death.4 The Rapid Murine Coma and Behavior Scale (RMCBS) is a helpful score to evaluate clinical symptoms of ECM. It consists of 10 parameters, each scored from 0 to 2, with a maximum possible score of 20.6 Recently, we showed good agreement between the severity of the RMCBS scores in ECM mice and pathological changes demonstrated by MRI.7 In this protocol, we describe ECM induction in mice and in vivo magnetic resonance imaging of mice with ECM.

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			<td colspan="2">FMRIB&#39;s Software Library</td>
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in vivo tracking of edema development and microvascular pathology in a model of experimental cerebral malaria using magnetic resonance imaging

Cerebral malaria is a sign of severe malarial disease and is often a harbinger of death. While aggressive management can be life-saving, the detection of cerebral malaria can be difficult. We present an experimental mouse model of cerebral malaria that shares multiple features of the human disease, including edema and microvascular pathology. Using magnetic resonance imaging (MRI), we can detect and track the blood-brain barrier disruption, edema development, and subsequent brain swelling. We describe multiple MRI techniques that can visualize these pertinent pathological changes. Thus, we show that MRI represents a valuable tool to visualize and track pathological changes, such as edema, brain swelling, and microvascular pathology, in vivo.

In C57BL/6 mice, the first clinical symptoms of ECM can be observed between days 6 and 10 after infection with P. berghei ANKA sporozoites. ECM develops in 60 - 80% of infected mice and rapidly progresses to coma and death within 24 to 48 h. In contrast, mice that do not develop ECM die after the second week post-infection from severe anemia due to hyperparasitemia.12
In MRI imaging, the earliest...

Watch this Scientific Journal Video about In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging at JoVE.com

In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging

We describe a mouse model of experimental cerebral malaria and show how inflammatory and microvascular pathology can be tracked in vivo using magnetic resonance imaging.

In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging

Cerebral malaria is a sign of severe malarial disease and is often a harbinger of death. While aggressive management can be life-saving, the detection of ...

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