Neurofunctional and neuroimaging readouts for designing a preclinical stem-cell therapy trial in experimental stroke.
Fiche publication
Date publication
mars 2022
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PO Chrystelle
Tous les auteurs :
Dumot C, Po C, Capin L, Hubert V, Ong E, Chourrout M, Bolbos R, Amaz C, Auxenfans C, Canet-Soulas E, Rome C, Chauveau F, Wiart M
Lien Pubmed
Résumé
With the aim of designing a preclinical study evaluating an intracerebral cell-based therapy for stroke, an observational study was performed in the rat suture model of ischemic stroke. Objectives were threefold: (i) to characterize neurofunctional and imaging readouts in the first weeks following transient ischemic stroke, according to lesion subtype (hypothalamic, striatal, corticostriatal); (ii) to confirm that intracerebral administration does not negatively impact these readouts; and (iii) to calculate sample sizes for a future therapeutic trial using these readouts as endpoints. Our results suggested that the most relevant endpoints were side bias (staircase test) and axial diffusivity (AD) (diffusion tensor imaging). Hypothalamic-only lesions did not affect those parameters, which were close to normal. Side bias in striatal lesions reached near-normal levels within 2 weeks, while rats with corticostriatal lesions remained impaired until week 14. AD values were decreased at 4 days and increased at 5 weeks post-surgery, with a subtype gradient: hypothalamic < striatal < corticostriatal. Intracerebral administration did not impact these readouts. After sample size calculation (18-147 rats per group according to the endpoint considered), we conclude that a therapeutic trial based on both readouts would be feasible only in the framework of a multicenter trial.
Référence
Sci Rep. 2022 Mar 18;12(1):4700