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 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.