Combinational Approach of Genetic SHP-1 Suppression and Voluntary Exercise Promotes Corticospinal Tract Sprouting and Motor Recovery Following Brain Injury.
Neurorehabil Neural Repair
; 34(6): 558-570, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32441214
ABSTRACT
Background. Brain injury often causes severe motor dysfunction, leading to difficulties with living a self-reliant social life. Injured neural circuits must be reconstructed to restore functions, but the adult brain is limited in its ability to restore neuronal connections. The combination of molecular targeting, which enhances neural plasticity, and rehabilitative motor exercise is an important therapeutic approach to promote neuronal rewiring in the spared circuits and motor recovery. Objective. We tested whether genetic reduction of Src homology 2-containing phosphatase-1 (SHP-1), an inhibitor of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, has synergistic effects with rehabilitative training to promote reorganization of motor circuits and functional recovery in a mouse model of brain injury. Methods. Rewiring of the corticospinal circuit was examined using neuronal tracers following unilateral cortical injury in control mice and in Shp-1 mutant mice subjected to voluntary exercise. Recovery of motor functions was assessed using motor behavior tests. Results. We found that rehabilitative exercise decreased SHP-1 and increased BDNF and TrkB expression in the contralesional motor cortex after the injury. Genetic reduction of SHP-1 and voluntary exercise significantly increased sprouting of corticospinal tract axons and enhanced motor recovery in the impaired forelimb. Conclusions. Our data demonstrate that combining voluntary exercise and SHP-1 suppression promotes motor recovery and neural circuit reorganization after brain injury.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Condicionamento Físico Animal
/
Tratos Piramidais
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Lesões Encefálicas
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Recuperação de Função Fisiológica
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Proteína Tirosina Fosfatase não Receptora Tipo 6
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Atividade Motora
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Córtex Motor
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurorehabil Neural Repair
Assunto da revista:
NEUROLOGIA
/
REABILITACAO
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão