| Title: |
Systems-based identification of new adjunct therapies for treatment of malaria-induced cerebral pathology |
| Authors: |
Strangward, Patrick; Couper, Kevin |
| Source: |
The Journal of Immunology ; volume 196, issue 1_Supplement, page 134.13-134.13 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2016 |
| Description: |
Cerebral Malaria (CM) is a severe neurological complication of Plasmodium falciparum infection characterised by abnormal posturing, seizures and coma. Current treatment involves the administration of anti-parasitic drugs, and fails to prevent mortality in 10–20% of cases. Furthermore, up to a quarter of effectively treated individuals exhibit long-term neurological dysfunction after an episode of CM. Crucially, we lack understanding of the factors that govern a successful or unsuccessful outcome to current treatment. Therefore, the aim of this study was to utilise the murine experimental model of CM (ECM) to further our understanding of the mechanism(s) that determine successful drug therapy of CM, in order to aid development of specific adjunct therapies. C57BL/6 mice were infected with Plasmodium berghei ANKA and then treated with anti-parasitic drugs at the onset of mild neurological dysfunction. Survival was ~80% in drug treated mice, with histological examination indicating attenuation of oedema as a key feature in mice that respond successfully to drug therapy. Additionally, whole brain transcriptomics demonstrated unique cerebral RNA signatures in mice at the point of drug treatment, post successful drug treatment and in the absence of drug treatment. Moreover, these data implicated several pathways relating to endothelial permeability as significant in mice that succumb to ECM. The results of this study provide important new information on pathways amenable to therapeutic modulation to aid treatment of CM. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.196.supp.134.13 |
| Availability: |
https://doi.org/10.4049/jimmunol.196.supp.134.13; https://academic.oup.com/jimmunol/article/196/1_Supplement/134.13/7963084 |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.16E52A66 |
| Database: |
BASE |