Fingolimod inhibits brain atrophy and promotes brain-derived neurotrophic factor in an animal model of multiple sclerosis.
J Neuroimmunol
; 318: 103-113, 2018 05 15.
Article
en En
| MEDLINE
| ID: mdl-29530550
ABSTRACT
Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7â¯Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain. Serial brain MRI measurements revealed slow progressive brain volume loss in vehicle treated EAE mice despite a stable clinical score. Fingolimod (1â¯mg/kg) significantly ameliorated brain tissue atrophy in the cerebellum and striatum when administered from established EAE disease onwards. Fingolimod-dependent tissue preservation was associated with induction of BDNF specifically within the brain and co-localized with neuronal soma. In contrast, therapeutic teriflunomide (3â¯mg/kg) treatment failed to inhibit CNS autoimmune mediated brain degeneration. Finally, weekly anti-IL-17A antibody (15â¯mg/kg) treatment was highly efficacious and preserved whole brain, cerebellum and striatum volume. Fingolimod-mediated BDNF increases within the CNS may contribute to limiting progressive tissue loss during chronic neuroinflammation.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Factor Neurotrófico Derivado del Encéfalo
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Encefalomielitis Autoinmune Experimental
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Clorhidrato de Fingolimod
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Inmunosupresores
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neuroimmunol
Año:
2018
Tipo del documento:
Article