Pathophysiology of Cerebral Malaria: Implications of MSCs as A Regenerative Medicinal Tool
Amrendra Chaudhary1, Poonam Kataria1, Neha Surela1
1Parasite-Host Biology, National Institute of Malaria Research, New Delhi 110077, India.
Abstract:
The severe form of malaria, i.e., cerebral malaria caused by Plasmodium falciparum, is a complex neurological syndrome. Surviving persons have a risk of behavioral difficulties, cognitive disorders, and epilepsy. Cerebral malaria is associated with multiple organ dysfunctions. The adhesion and accumulation of infected RBCs, platelets, and leucocytes (macrophages, CD4+ and CD8+ T cells, and monocytes) in the brain microvessels play an essential role in disease progression. Micro-vascular hindrance by coagulation and endothelial dysfunction contributes to neurological damage and the severity of the disease. Recent studies in human cerebral malaria and the murine model of cerebral malaria indicate that different pathogens as well as host-derived factors are involved in brain microvessel adhesion and coagulation that induces changes in vascular permeability and impairment of the blood-brain barrier. Efforts to alleviate blood-brain barrier dysfunction and de-sequestering of RBCs could serve as adjunct therapies. In this review, we briefly summarize the current understanding of the pathogenesis of cerebral malaria, the role of some factors (NK cells, platelet, ANG-2/ANG-1 ratio, and PfEMP1) in disease progression and various functions of Mesenchymal stem cells. This review also highlighted the implications of MSCs as a regenerative medicine.
Insights
Cerebral malaria, a severe Plasmodium falciparum complication, causes neurological damage via brain microvessel adhesion and dysfunction. Mesenchymal stem cells (MSCs) show promise as a regenerative therapy for this condition.
Area of Science:
- Neurology
- Immunology
- Infectious Diseases
Background:
- Cerebral malaria (CM), a severe Plasmodium falciparum complication, presents as a complex neurological syndrome.
- CM survivors face risks of cognitive deficits, behavioral issues, and epilepsy, alongside multi-organ dysfunction.
- Pathogenesis involves infected red blood cell (RBC) adhesion, immune cell accumulation, and coagulation in brain microvasculature, leading to endothelial dysfunction and blood-brain barrier (BBB) impairment.
Purpose of the Study:
- To review the current understanding of cerebral malaria pathogenesis.
- To explore the roles of specific factors like NK cells, platelets, ANG-2/ANG-1 ratio, and PfEMP1 in disease progression.
- To highlight the potential of Mesenchymal stem cells (MSCs) in regenerative medicine for CM.
Main Methods:
- This is a review article, synthesizing existing research on cerebral malaria.
- It examines studies on human CM and murine models.
- It focuses on the molecular and cellular mechanisms underlying CM pathology and potential therapeutic strategies.
Main Results:
- Brain microvessel adhesion and coagulation, influenced by pathogens and host factors, are critical in CM.
- Endothelial dysfunction and BBB impairment contribute significantly to neurological damage.
- Mesenchymal stem cells (MSCs) demonstrate potential therapeutic functions relevant to CM.
Conclusions:
- Alleviating BBB dysfunction and promoting RBC de-sequestration are potential adjunct therapies for CM.
- Understanding the roles of specific immune cells and molecular factors is crucial for CM management.
- Mesenchymal stem cells (MSCs) represent a promising avenue for regenerative therapy in cerebral malaria.
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