Vagus nerve stimulation enhances remyelination and decreases innate neuroinflammation in lysolecithin-induced demyelination.
Brain Stimul
; 17(3): 575-587, 2024.
Article
en En
| MEDLINE
| ID: mdl-38648972
ABSTRACT
BACKGROUND:
Current treatments for Multiple Sclerosis (MS) poorly address chronic innate neuroinflammation nor do they offer effective remyelination. The vagus nerve has a strong regulatory role in inflammation and Vagus Nerve Stimulation (VNS) has potential to affect both neuroinflammation and remyelination in MS.OBJECTIVE:
This study investigated the effects of VNS on demyelination and innate neuroinflammation in a validated MS rodent model.METHODS:
Lysolecithin (LPC) was injected in the corpus callosum (CC) of 46 Lewis rats, inducing a demyelinated lesion. 33/46 rats received continuously-cycled VNS (cVNS) or one-minute per day VNS (1minVNS) or sham VNS from 2 days before LPC-injection until perfusion at 3 days post-injection (dpi) (corresponding with a demyelinated lesion with peak inflammation). 13/46 rats received cVNS or sham from 2 days before LPC-injection until perfusion at 11 dpi (corresponding with a partial remyelinated lesion). Immunohistochemistry and proteomics analyses were performed to investigate the extend of demyelination and inflammation.RESULTS:
Immunohistochemistry showed that cVNS significantly reduced microglial and astrocytic activation in the lesion and lesion border, and significantly reduced the Olig2+ cell count at 3 dpi. Furthermore, cVNS significantly improved remyelination with 57.4 % versus sham at 11 dpi. Proteomic gene set enrichment analyses showed increased activation of (glutamatergic) synapse pathways in cVNS versus sham, most pronounced at 3 dpi.CONCLUSION:
cVNS improved remyelination of an LPC-induced lesion. Possible mechanisms might include modulation of microglia and astrocyte activity, increased (glutamatergic) synapses and enhanced oligodendrocyte clearance after initial injury.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ratas Endogámicas Lew
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Lisofosfatidilcolinas
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Enfermedades Desmielinizantes
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Estimulación del Nervio Vago
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Remielinización
Límite:
Animals
Idioma:
En
Revista:
Brain Stimul
Asunto de la revista:
CEREBRO
Año:
2024
Tipo del documento:
Article