title: In silico study of the influence of intensity and duration of blood flow reduction on cell death through necrosis or apoptosis during acute ischemic stroke.
abstract: Ischemic stroke involves numerous and complex pathophysiological mechanisms including blood flow reduction, ionic exchanges, spreading depressions and cell death through necrosis or apoptosis. We used a mathematical model based on these phenomena to study the influences of intensity and duration of ischemia on the final size of the infarcted area. This model relies on a set of ordinary and partial differential equations. After a sensibility study, the model was used to carry out in silico experiments in various ischemic conditions. The simulation results show that the proportion of apoptotic cells increases when the intensity of ischemia decreases, which contributes to the model validation. The simulation results also show that the influence of ischemia duration on the infarct size is more complicated. They suggest that reperfusion is beneficial when performed in the early stroke but may be either inefficacious or even deleterious when performed later after the stroke onset. This aggravation could be explained by the depolarisation waves which might continue to spread ischemic damage and by the speeding up of the apoptotic process leading to cell death. The effect of reperfusion on cell death through these two phenomena needs to be further studied in order to develop new therapeutic strategies for stroke patients.
authors.affiliation: Université Paul Cézanne, Faculté St Jérôme, Case Cour A, av. Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France. guillemette.chapuisat@univ-cezanne.fr
authors.forename: Guillemette
authors.initials: G
authors.lastname: Chapuisat
authors.forename: Marie-Aimée
authors.initials: MA
authors.lastname: Dronne
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Grenier
authors.forename: Marc
authors.initials: M
authors.lastname: Hommel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Boissel
mesh_terms: D000465:Algorithms; D017209:Apoptosis; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D006801:Humans; D008955:Models, Cardiovascular; D008959:Models, Neurological; D009336:Necrosis; D012039:Regional Blood Flow; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors