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Early intensive rehabilitation reverses locomotor disruption, decrease brain inflammation and induces neuroplasticity following experimental Cerebral Palsy.
Sanches, Eduardo; Ho, Dini; van de Looij, Yohan; Aebi Toulotte, Audrey; Baud, Laetitia; Bouteldja, Farha; Barraud, Quentin; Araneda, Rodrigo; Bleyenheuft, Yannick; Brochard, Sylvain; Kathe, Claudia; Courtine, Grégoire; Sizonenko, Stéphane.
Afiliación
  • Sanches E; Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland.
  • Ho D; Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland.
  • van de Looij Y; Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland; Center for Biomedical Imaging (CIBM), Animal Imaging Technology Section, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Aebi Toulotte A; Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland.
  • Baud L; Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland; NeuroX Institute and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland; Department of Clinical Neuroscience, Lausanne University H
  • Bouteldja F; Department of Fundamental Neurosciences, University of Lausanne (Unil), Switzerland.
  • Barraud Q; Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland; NeuroX Institute and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland; Department of Clinical Neuroscience, Lausanne University H
  • Araneda R; Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium; Exercise and Rehabilitation Science Institute, Faculty of Rehabilitation Science, Universidad Andres Bello, Santiago, Chile.
  • Bleyenheuft Y; Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
  • Brochard S; Physical and Medical Rehabilitation Department, CHRU Brest, Brest, France; Paediatric Physical and Medical Rehabilitation Department, Fondation ILDYS, Brest, France; University of Western Brittany, Laboratory of Medical Information Processing, Inserm U1101, Brest, France.
  • Kathe C; Department of Fundamental Neurosciences, University of Lausanne (Unil), Switzerland.
  • Courtine G; Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland; NeuroX Institute and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland; Department of Clinical Neuroscience, Lausanne University H
  • Sizonenko S; Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Stephane.Sizonenko@hcuge.ch.
Brain Behav Immun ; 121: 303-316, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39098438
ABSTRACT

BACKGROUND:

Cerebral Palsy (CP) is a major cause of motor and cognitive disability in children due to injury to the developing brain. Early intensive sensorimotor rehabilitation has been shown to change brain structure and reduce CP symptoms severity. We combined environmental enrichment (EE) and treadmill training (TT) to observe the effects of a one-week program of sensorimotor stimulation (EETT) in animals exposed to a CP model and explored possible mechanisms involved in the functional recovery.

METHODS:

Pregnant Wistar rats were injected with Lipopolysaccharide (LPS - 200 µg/kg) intraperitoneally at embryonic days 18 and 19. At P0, pups of both sexes were exposed to 20' anoxia at 37 °C. From P2 to P21, hindlimbs were restricted for 16 h/day during the dark cycle. EETT lasted from P21 to P27. TT - 15 min/day at 7 cm/s. EE - 7 days in enriched cages with sensorimotor stimulus. Functional 3D kinematic gait analysis and locomotion were analyzed. At P28, brains were collected for ex-vivo MRI and histological assessment. Neurotrophins and key proteins involved in CNS function were assessed by western blotting.

RESULTS:

CP model caused gross and skilled locomotor disruption and altered CNS neurochemistry. EETT reversed locomotor dysfunction with minor effects over gait kinematics. EETT also decreased brain inflammation and glial activation, preserved myelination, upregulated BDNF signaling and modulated the expression of proteins involved in excitatory synaptic function in the brain and spinal cord.

CONCLUSIONS:

Using this translational approach based on intensive sensorimotor rehabilitation, we highlight pathways engaged in the early developmental processes improving neurological recovery observed in CP.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Parálisis Cerebral / Ratas Wistar / Modelos Animales de Enfermedad / Locomoción / Plasticidad Neuronal Límite: Animals / Pregnancy Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Parálisis Cerebral / Ratas Wistar / Modelos Animales de Enfermedad / Locomoción / Plasticidad Neuronal Límite: Animals / Pregnancy Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Países Bajos