Related Experiment Video
Updated: Jun 22, 2026
Isolation and Analysis of Brain-sequestered Leukocytes from Plasmodium berghei ANKA-infected Mice
Published on: January 2, 2013
Histamine H(3) receptor-mediated signaling protects mice from cerebral malaria
Walid Beghdadi1, Adeline Porcherie, Bradley S Schneider
1Unité des Réponses Précoces aux Parasites et Immunopathologie, Institut Pasteur, Paris, France.
Background:
Histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. In humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. We reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (CM) in mice infected with Plasmodium berghei ANKA. Histamine exerts its biological effects through four different receptors designated H1R, H2R, H3R, and H4R.
Principal Findings:
In the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R) in the pathogenesis of murine CM. We observed that the lack of H3R expression (H3R(-/-) mice) accelerates the onset of CM and this was correlated with enhanced brain pathology and earlier and more pronounced loss of blood brain barrier integrity than in wild type mice. Additionally tele-methylhistamine, the major histamine metabolite in the brain, that was initially present at a higher level in the brain of H3R(-/-) mice was depleted more quickly post-infection in H3R(-/-) mice as compared to wild-type counterparts.
Conclusions:
Our data suggest that histamine regulation through the H3R in the brain suppresses the development of CM. Thus modulating histamine signaling in the central nervous system, in combination with standard therapies, may represent a novel strategy to reduce the risk of progression to cerebral malaria.
Insights
Histamine H3 receptor (H3R) signaling in the brain suppresses experimental cerebral malaria (CM) development. Lack of H3R accelerates CM, suggesting H3R modulation as a potential therapeutic strategy for this severe malaria complication.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Pharmacology
Background:
- Histamine contributes to pathological conditions like malaria.
- Elevated histamine levels correlate with malaria severity in humans and murine models.
- Histamine acts via four receptors: H1R, H2R, H3R, and H4R.
Purpose of the Study:
- To investigate the role of histamine signaling through the histamine H3 receptor (H3R) in the pathogenesis of experimental cerebral malaria (CM).
Main Methods:
- Utilized H3R knockout (H3R(-/-)) mice and wild-type (WT) mice infected with Plasmodium berghei ANKA.
- Assessed CM onset, brain pathology, and blood-brain barrier integrity.
- Measured tele-methylhistamine levels in the brain.
Main Results:
- H3R(-/-) mice exhibited accelerated CM onset compared to WT mice.
- Lack of H3R led to enhanced brain pathology and earlier, more pronounced blood-brain barrier disruption.
- Tele-methylhistamine, initially higher in H3R(-/-) mice, was depleted faster post-infection.
Conclusions:
- Histamine regulation via H3R in the brain appears to suppress CM development.
- Modulating central nervous system histamine signaling may offer a novel therapeutic approach for cerebral malaria.
- Targeting H3R could reduce the risk of progression to severe CM.
