Section: Application Domains
Stroke is a very complex pathology, involving many different time scales and phenomena. Numed is currently developping various models to describe some important aspects of stroke.
MA Dronne has designed a first model of inflammation at cellular level, based on ordinary differential equations. To take into account spatial phenomena, a first partial differential equation based model is under study. Together with Taissia Lelekov Boissard (post doc of the ANR contrat "AVC in silico"), they tried to find biological data to parametrize these models, and to build a basis of qualitative facts that must be reproduced by the model.
MA Dronne has also developped a collaboration with the Mario Negri institute (Milano) through the team "inflammation and nervous system diseases" (MG de Simoni). This teams currently runs in vivo experiments in rodent that should provide new data to investigate the temporal evolution of various variables of the model.
The study and validation of these two models of inflammation will continue with the study of in silico experiments which will simulate the action of various anti inflammatory drugs, acting at various levels of the inflammatory reaction, work in common with biologists (INSERM 842, neurooncologie et neuro inflammation, Lyon), with clinicians (Creatis, Umr 5515, Inserm U 630 Lyon).
A first model of free radical synthesis has been initiated by V. Lemesle (post doc of ANR AVC in silico). This model is under developpment with P. Vigneaux. A collaboration begins with Michel Plotkine (EA 2510 pharmacology of cerebral blood flow, Paris 5 university) to get experimental data on the temporal evolution of the various variables of the model.
This model will be used to manage in silico experiments in order to study the effects of various drugs.
A mechanistic model of ionic motions has already been developped, studied and validated to study in silico the dual role of astrocytes during ischemia, and to study the effect of various ionic chanels blockers in man and roden.
This model is now used to study in silico the effect of the combination of several neuroprotectors acting on ionic channels, transporters or receptors. This work should help to understand antagonist or synergic effects of blockers.
Spreading depressions are propagative waves which travel in brain during ischemia and which may have a major role in the extension of the ischemic core. Currently 3D computations in real geometry are run to study their speed and the role of brain anatomy in their propagation.
Apoptosis during stroke
A collaboration has begun with Christiane Charriaut Marlangue (INSERM U676, Hopital Robert Debré) to study the apoptotic cascade during stroke.