Abstract
Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In the present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 μL of whole blood along with 20 mg/kg of artemether. ECM mice showed severe thrombocytopenia and decreases in hematocrit. Artemether treatment markedly aggravated anemia within 24 h. Whole blood administration significantly prevented further drop in hematocrit and partially restored the platelet count. Increased levels of plasma angiopoietin-2 (Ang-2) remained high 24 h after artemether treatment but returned to normal levels 24 h after blood transfusion, indicating reversal to quiescence. Ang-1 was depleted in ECM mice and levels were not restored by any treatment. Blood transfusion prevented the aggravation of the breakdown of blood brain barrier after artemether treatment and decreased spleen congestion without affecting splenic lymphocyte populations. Critically, blood transfusion resulted in markedly improved survival of mice with ECM (75.9% compared to 50.9% receiving artemether only). These findings indicate that whole blood transfusion can be an effective adjuvant therapy for cerebral malaria.
Highlights
Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components
A well-characterized and commonly used experimental model for cerebral malaria (ECM), C57BL/6 mice infected with P. berghei ANKA (PbA)[21,22], was used to investigate the effects of whole blood transfusion as adjunctive therapy to artemether in the late stages of the disease
Preliminary experiments were performed in order to define the feasibility of blood transfusion via intraperitoneal injection, as d escribed[31], and to define a suitable treatment to compare with the performance of artemether plus whole blood transfusion in late-stage ECM
Summary
Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. A well-characterized and commonly used experimental model for cerebral malaria (ECM), C57BL/6 mice infected with P. berghei ANKA (PbA)[21,22], was used to investigate the effects of whole blood transfusion as adjunctive therapy to artemether in the late stages of the disease This experimental model shows a number of similarities with human CM as well as some differences. Feature of the neurological syndrome, but P. berghei-infected erythrocyte accumulation in the brain has been documented and a recent study showed that P. berghei-infected erythrocytes are trapped in brain capillaries and contribute to impaired cerebral blood flow[27,28,29] In both human and experimental CM, cerebrovascular blockage and severe vasculopathy occur, making this model appropriate to investigate interventions intended to restore vascular function, cerebral blood flow and cerebral oxygenation.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
