title: Strength and fine dexterity recovery profiles after a primary motor cortex insult and effect of a neuronal cell graft.
abstract: The aim of this study was to set up (a) a large primary motor cortex (M1) lesion in rodent and (b) the conditions for evaluating a long-lasting motor deficit in order to propose a valid model to test neuronal replacement therapies aimed at improving motor deficit recovery. A mitochondrial toxin, malonate, was injected to induce extensive destruction of the forelimb M1 cortex. Three key motor functions that are usually evaluated following cerebral lesion in the clinic-strength, target reaching, and fine dexterity-were assessed in rats by 2 tests, a forelimb grip strength test and a skilled reaching task (staircase) for reaching and dexterity. The potential enhancement of postlesion recovery induced by a neuronal cell transplantation was then explored and confirmed by histological analyses. Both tests showed a severe functional impairment 2 days post lesion, however, reaching remained intact. Deficits in forelimb strength were long lasting (up to 3 months) but spontaneously recovered despite the extensive lesion size. This natural grip strength recovery could be enhanced by cell therapy. Histological analyses confirmed the presence of grafted cells 3 months postgraft and showed partial tissue reconstruction with some living neuronal cells in the graft. In contrast, fine dexterity never recovered in the staircase test even after grafting. These results suggest that cell replacement was only partially effective and that the forelimb M1 area may be a node of the sensorimotor network, where compensation from secondary pathways could account for strength recovery but recovery of forelimb fine dexterity requires extensive tissue reconstruction.
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vaysse
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Conchou
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Boris
authors.initials: B
authors.lastname: Demain
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Carole
authors.initials: C
authors.lastname: Davoust
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Plas
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Ruggieri
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Benkaddour
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Marion
authors.initials: M
authors.lastname: Simonetta-Moreau
authors.affiliation: Inserm, Imagerie cérébrale et handicaps neurologiques UMR 825.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Loubinoux
mesh_terms: D000818:Animals; D002460:Cell Line; D005552:Forelimb; D018737:Hand Strength; D064593:Heterografts; D006801:Humans; D008297:Male; D008314:Malonates / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D009044:Motor Cortex / Q000187:drug effects / Q000473:pathology* / Q000601:surgery*; D009048:Motor Skills / Q000187:drug effects; D009474:Neurons / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: D008314:Malonates; C030290:malonic acid