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In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging
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Increased brain microvascular hemoglobin concentrations in children with cerebral malaria

Rachel L Smith1, Allison K Ikeda1, Carol A Rowley1

  • 1Physiology Unit, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.

Science Translational Medicine
|September 13, 2023
PubMed

Insights

Brain swelling in cerebral malaria may be caused by vascular congestion, not just edema. Near-infrared spectroscopy revealed higher hemoglobin concentrations and impaired blood flow regulation in affected children, correlating with brain swelling.

Area of Science:

  • Neuroscience
  • Hematology
  • Pediatric Infectious Diseases

Background:

  • Cerebral malaria is a severe complication of *Plasmodium falciparum* infection, often leading to fatal brain swelling.
  • The exact cause of brain swelling in cerebral malaria, whether cerebral edema or vascular congestion, remains unclear.
  • Distinct pathological mechanisms have different implications for tissue hemoglobin concentration and cerebral blood flow.

Purpose of the Study:

  • To investigate the role of cerebral microvascular hemoglobin concentrations in children with cerebral malaria.
  • To differentiate between cerebral edema and vascular congestion as causes of brain swelling using non-invasive techniques.
  • To assess cerebral blood flow regulation in pediatric cerebral malaria.

Main Methods:

  • Near-infrared spectroscopy (NIRS) was employed to noninvasively measure cerebral microvascular hemoglobin concentrations in 46 Malawian children with cerebral malaria.
  • Control groups included children with uncomplicated malaria (n=33) and healthy children (n=29).
  • Detrended fluctuation analysis (DFA) characterized signal self-similarity to assess cerebral blood flow regulation, and MRI determined brain swelling scores.

Main Results:

  • Children with cerebral malaria exhibited significantly higher cerebral microvascular hemoglobin concentrations (145.2 μM) compared to those with uncomplicated malaria (82.9 μM) (P=0.008).
  • Cerebral microvascular hemoglobin concentrations positively correlated with brain swelling scores determined by MRI (r=0.37, P=0.03).
  • Detrended fluctuation analysis revealed lower self-similarity in hemoglobin concentration signals among children with cerebral malaria (0.63) versus uncomplicated malaria (0.91) (P<0.0001), indicating impaired cerebral blood flow regulation.

Conclusions:

  • Elevated cerebral tissue hemoglobin concentration in cerebral malaria suggests that increased blood volume, likely due to vascular congestion, contributes to brain swelling.
  • Impaired self-similarity of hemoglobin concentration signals indicates dysregulation of cerebral blood flow in cerebral malaria.
  • Non-invasive NIRS can provide insights into the pathophysiology of brain swelling in pediatric cerebral malaria.

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