Methotrexate carried in lipid core nanoparticles reduces microglial activation and induces neuroprotection after cortical stroke induced in rats

Background This study aimed to investigate the effects of LDE-MTX on acute cerebral infarction. The study focuses on how LDE-MTX can influence the outcomes of ischemic stroke in a rat model, specifically examining its neuroprotective properties. Methods Radioactively labeled LDE uptake by brain tiss...

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Detalles Bibliográficos
Autores: Pereira, Edmundo L. R., Maranhão, Raul C., Dias, Michelle N. C., Santos, Ijair R. dos, Santos, Carolina Ramos dos, Hamoy, Mois´es, Feio , Danielle Cristine A., Carvalho, Priscila O., Bazioli, Jaqueline M., Morikawa, Aleksandra T., Gomes-Leal, Walace
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:Brasil
Institución:Universidade de São Paulo (USP)
Repositorio:Clinics
Idioma:inglés
OAI Identifier:oai:revistas.usp.br:article/238898
Acceso en línea:https://revistas.usp.br/clinics/article/view/238898
Access Level:acceso abierto
Palabra clave:Drug delivery
Neuroinflammation
Neuroprotection
Methotrexate (Methotrexate)
Solid lipid nanoparticles
Descripción
Sumario:Background This study aimed to investigate the effects of LDE-MTX on acute cerebral infarction. The study focuses on how LDE-MTX can influence the outcomes of ischemic stroke in a rat model, specifically examining its neuroprotective properties. Methods Radioactively labeled LDE uptake by brain tissue was determined after IV injection in rats with Endothelin-1 (ET-1)-induced cortical ischemic stroke (n = 11) and controls (n = 18). Two groups of 5 animals were treated with LDE-MTX (1 mg/kg, IV) or LDE-alone 4 h post-stroke induction. After 7days, tissues were analyzed by immunohistochemistry for neuronal bodies, astrocytes, and microglia. Results LDE uptake was fivefold higher in ischemic rats than in controls (p = 0.0003). LDE-MTX significantly inhibited microglial activation, resulting in a tenfold decrease in activated macrophages, and increased neuronal survival by 319% in the periinfarct area. LDE-MTX had no effect on astrocytosis or primary infarct size. Conclusions LDE-MTX demonstrated neuroprotective effects and shows potential as a novel strategy to limit ischemic stroke damage. The results suggest that LDE-MTX could be a promising treatment option for reducing ischemic damage in stroke patients, particularly through its effect on microglial activation and neuronal survival.

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