Neurometabolic sequelae of experimental cerebral malaria

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master's degree in a non-French university. 

This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details.

State of the art: Malaria accounted for 282 million cases and 610 000 deaths in 2024 (WHO, 2025), mostly due to cerebral malaria (CM), the deadliest complication of Plasmodium falciparum infection. CM is characterized by seizures and coma. Survivors may develop neurological deficits affecting memory, sensory, motor, or executive functions that are understudied (4). The mouse model of CM, a good model of human CM, has helped reconcile controversies such as the presence of brain oedema, now known as a major determinant of human CM progression (1-3). Our team studies the sequelae of murine CM with survival using advanced MRI and MR spectroscopy (MRS) methods. We have identified several neurometabolic anomalies, one of them affecting glucose, the major brain fuel (5). 

Objective : Our aim is to confirm the results on glucose and identify the mechanisms causing reduced glucose brain level and increased uptake detected using 1H-MRS and positron emission tomography (PET, collaboration with CERIMED). We hypothesise that these results could reflect hypermetabolism, possibly linked to residual inflammation months after CM resolution. 

Methods: Female and male C57BL/6 and CBA/J mice inoculated with PbA will be treated by chloroquine during 10 days from CM peak and explored during 4 months by a multimodal approach. [18F]FDG PET will be used for the estimation of glucose uptake and 2H-MRS with [6,6’-2H2]glucose will enable the study of glucose metabolism (6). MRI with Gd-DOTA and PET with 18F-DPA714 will be used to assess blood brain barrier permeability and glial/microglial activation. Histological studies of brain microvasculature and neuroinflammation will be performed in collaboration with Dr Boudewijn Van der Sanden (TIMC UMR 5525, CNRS-Grenoble INP-Université Grenoble Alpes).

Expected results:  This approach should enable us to confirm hypermetabolism and verify several mechanistic hypotheses such as residual inflammation and/or astrogliosis, or defective glycolysis.  

Feasibility:  We have the murine model of CM with survival. We have already constructed a deuterium dedicated RF coil for 2H-MRS of the mouse brain. We have set up all the MRI/MRS methods and have established a collaboration with Prs Benjmain Guillet and Philippe Garrigue (CERIMED) for the PET studies. The project is supported by Marseille Imaging Institute (Calls for Projects, Recherche 2026). We have an authorization for the study of brain sequelae in CM (APAFIS #38747), another DAP will be submitted next week to the CEEA Marseille 14 and 71 to cover new imaging studies. 

Within Aix Marseille Université, NeuroMarseille brings together 8 research laboratories and NeuroSchool, a graduate school in neuroscience, to increase the attractiveness of the university, international collaborations, interdisciplinarity, links with the clinical and industrial worlds and the integration of students into professional life. 

Launched in July 2018, NeuroSchool unifies and harmonizes the training of the third year of the Bachelor of Life Sciences (Neuroscience track), the Master's and the PhD in Neuroscience. 

• Expected candidate profile : We are looking for a highly motivated student with background in brain anatomy and neurometabolism, an interest in imaging, and hands-on experience with animal use in scientific procedures.