Dear Pandora and Rebecca,We were quite interested by your paper "Are researchers moving away from animal models as a result of poor clinical translation in the field of stroke? An analysis of opinion papers" (BMJ Open Science, 2020). Thank for this illuminating work which makes concrete what we had in mind since a work published in 2004-2007 (Dronne MA, Boissel JP, Grenier E, Gilquin H, Cucherat M, Hommel M, Barbier E, Bricca G. Mathematical modelling of an ischemic stroke: an integrative approach. Acta Biotheor. 2004;52:255-72; Dronne M.A., Boissel J.P., Grenier E., A mathematical model of ion movements in grey matter during a stroke. J Theor Biol 2006;240:599-615; 247. Dronne MA, Grenier E, Dumont T, Hommel M, Boissel JP. Role of astrocytes in grey matter during stroke: A modelling approach. Brain Res. 2007;1138:231-42; 252. Dronne MA, Grenier E, Chapuisat G, Hommel M, Boissel JP. A modelling approach to explore some hypotheses of the failure of neuroprotective trials in ischemic stroke patients. Prog Biophys Mol Biol. 2008. Grenier E, Dronne MA, Descombes S, Gilquin H, Jaillard A, Hommel M, Boissel JP. A numerical study of the blocking of migraine by Rolando sulcus. Prog Biophys Mol Biol. 2008). At this time there were circa 300 "neuroprotective" agents that had worked on rodent models and failed when tested in stroke patients. We used a mathematical model of acute stroke with a rodent and a human versions. Our simulations showed that drugs reducing infarct size in rodents in silico model did not reduce it (or even increase it) in human in silico model. This in silico investigation suggests that the proportions of glial cells and white matter have an influence on neuroprotective drug efficacy. In another work we showed that gyrocephaly in Humans compared to lissenphaly in rodents may also make the difference. These results reinforce the hypothesis that histological and morphological differences between rodent and human brains can partly explain the failure of these agents in clinical trials. The survey you made showed that 1) animal model paradigm in acute ischemic stroke is still alive and its supporters believe it can be improved, and 2) for those who dismiss it, the only alternative is in vitro models based on human material. We suggest that a third alternative exists, the in silico M&S (Modelling and Simulation).