Cerebral malaria, a syndrome found in patients infected with Plasmodium falciparum, kills an estimated 2 million children a year. The lack of an animal model has been a barrier to research into supportive therapies and treatment . We are developing a model of this condition in rhesus monkeys inoculated with P. knowlesi, a simian malaria parasite. As the condition is thought to be caused by parasitized red cells adhering to the cerebral endothelium, we have cultured rhesus brain endothelium in vitro and added blood cells containing parasites. We have used a cytokine (TNFa) to stimulate the receptors on the cultured brain endothelium and increase the number of adherent red cells. We have now selected a population of parasites that consistently adhere to brain endothelium and we will next put these parasites back into a rhesus monkey to produce cerebral malaria. Once this sydrome has been seen in the experimental animals, we will be able to test treatments and supportive therapies that can be taken to endemic areas for use in children afflicted with this condition. FUNDING Base Grant, Venture Research PUBLICATIONS Handali S, Krogstad FM, Philipps J, Didier PJ, Cogswell FB and Krogstad DJ. Cytoadherence of Plasmodium Knowlesi-Infected Red Blood Cells (RBCs) to Rhesus Brain Endotheilial Cells. 47th Annual Meeting of the American Society of Tropical Medicine and Hygiene [Abstract #372].

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-39
Application #
6311748
Study Section
Project Start
1978-06-01
Project End
2002-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
39
Fiscal Year
2000
Total Cost
$199,892
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

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