A mathematical model of ion movements in grey matter during a stroke.
The development of cytotoxic oedema during a stroke consists in cell swelling and shrinking of the extracellular space. This phenomenon is triggered by ion movements through voltage-gated channels, exchangers and pumps. During ischaemia, sodium, calcium and chloride enter the neurons whereas potassium and glutamate are expelled out of the cells. A mathematical model is proposed to represent the long-term dynamics of membrane potentials, cell volumes and ionic concentrations in intracellular and extracellular spaces during a stroke and to study the influence of each ionic current on cell swelling. The model relies on electrophysiological mechanisms and takes into account the behaviour of two types of cells: neurons and also astrocytes known to play a key role in the excitotoxic process in grey matter. The results obtained when a severe or a moderate ischaemia is simulated are consistent with those observed in the in vitro and in vivo experiments. As this model appears to be robust, it is used to perform illustrative simulations aimed at studying the effect of some channel blockers on cell swelling. This approach may help to explore new therapeutic strategies in order to reduce stroke damage.
Dronne
Marie-Aimée
MA
Service de Pharmacologie Clinique, EA 3736, Faculté de Médecine Laennec, Rue Guillaume Paradin, BP 8071, 69376 Lyon, cedex 08, France. md@upcl.univ-lyon1.fr
Boissel
Jean-Pierre
JP
Grenier
Emmanuel
E
D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology*; D016623:Ion Pumps / Q000502:physiology; D008564:Membrane Potentials; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism; D020521:Stroke / Q000150:complications / Q000378:metabolism*
D007473:Ion Channels; D016623:Ion Pumps; D049990:Membrane Transport Modulators