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Updated: Apr 20, 2026

In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging
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Fatal cerebral malaria: a venous efflux problem

Ute Frevert1, Adéla Nacer2

  • 1Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine New York, NY, USA.

Frontiers in Cellular and Infection Microbiology
|November 22, 2014
PubMed

Insights

Severe intracranial hypertension (IH) causes fatal respiratory arrest in cerebral malaria (CM). This study models CM, revealing how parasite sequestration or leukocyte adhesion increases intracranial pressure, leading to brainstem herniation and death.

Area of Science:

  • Pathology
  • Immunology
  • Neuroscience

Background:

  • Cerebral malaria (CM) in children often results in fatal respiratory arrest, with unclear underlying pathology.
  • Existing hypotheses for CM pathogenesis lack a unifying mechanism applicable to both human and experimental models.

Purpose of the Study:

  • To propose and validate a unifying model for CM pathogenesis centered on intracranial hypertension (IH).
  • To elucidate the mechanisms leading to fatal outcomes in experimental and human CM.

Main Methods:

  • Dynamic imaging of mice infected with Plasmodium berghei ANKA to model experimental CM.
  • Analysis of leukocyte adhesion in postcapillary venules (PCV) and its effect on venous blood flow.
  • Correlation of increased intracranial pressure (ICP) with cerebral edema formation.

Main Results:

  • Leukocyte adhesion in PCV was shown to impair venous blood flow, leading to increased ICP.
  • Increased ICP exacerbates cerebral edema, a key feature of both murine and pediatric CM.
  • The study proposes that cytoadherence in human CM and leukocyte arrest in murine CM converge on IH.

Conclusions:

  • A unified model of intracranial hypertension (IH) explains fatal respiratory arrest in cerebral malaria (CM).
  • This IH model reconciles distinct pathogenetic mechanisms in human and experimental CM.
  • The model provides a framework for understanding parasite-induced neuronal dysfunction and fatal outcomes in CM.
Keywords:
CD8+ T cellPlasmodiumbrain edemacytoadherenceintracranial hypertensionmacrophagepostcapillary venulevascular leakage

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