Unilateral cervical spinal cord injury induces bone loss and metabolic changes in non-human primates (Macaca fascicularis)
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Résumé
BACKGROUND/OBJECTIVE: The deleterious effects of chronic spinal cord injury (SCI) on the skeleton in rats, especially the lower extremities, has been proved previously. However, the long-term skeletal changes after SCI in non-human primates (NHP) have been scarcely studied. This study aimed to evaluate the bone loss in limbs and vertebrae and the bone metabolic changes in NHP after unilateral cervical spinal cord contusion injury. METHODS: were randomly divided into the SCI (n=8) and the Sham (n=4) groups. The SCI models were established using hemi-contusion cervical spinal cord injury on fifth cervical vertebra (C5), and were further evaluated by histological staining and neurophysiological monitoring. Changes of bone microstructures, bone biomechanics, and bone metabolism markers were assessed by micro-CT, micro-FEA and serological kit. RESULTS: The NHP hemi-contusion cervical SCI model led to consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord. Furthermore, the cancellous bone mass of ipsilateral humerus and radius decreased significantly compared to the contralateral side. The bone volume fraction of humerus and radius were 17.2% and 20.1% on the ipsilateral while 29.0% and 30.1% on the contralateral respectively. Similarly, the thickness of the cortical bone in the ipsilateral forelimbs was significantly decreased, as well as the bone strength of the ipsilateral forelimbs. These changes were accompanied by diminished concentration of osteocalcin and total procollagen type 1 N-terminal propeptide (t-P1NP) as well as increased level of β-C-terminal cross-linking telopeptide of type 1collagen (β-CTX) in serological testing. CONCLUSIONS: The present study demonstrated that hemi-SCI induced loss of bone mass and compromised biomechanical performance in ipsilateral forelimbs, which could be indicated by both muscle atrophy and serological changes of bone metabolism, and associated with a consistent loss of large-diameter cells of sensory neurons in the dorsal root ganglia. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study, for the first time, demonstrated the bone loss in limbs and vertebrae as well as the bone metabolic changes in non-human primates after unilateral spinal cord injury (SCI). This may help to elucidate the role of muscle atrophy, serological changes and loss of sensory neurons in the mechanisms of SCI-induced osteoporosis, which would be definitely better compared with rodent models.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle