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

## TL;DR

A new drug delivery method using lipid nanoparticles to carry methotrexate shows promise in reducing brain inflammation and protecting neurons after stroke in rats.

## Contribution

LDE-MTX significantly reduces microglial activation and boosts neuronal survival by 319% in a rat stroke model.

## Key findings

- LDE-MTX reduces microglial activation and macrophage count in rats.
- LDE-MTX increases neuronal survival by 319% in the periinfarct area.
- LDE-MTX shows no effect on astrocytosis or primary infarct size.

## Abstract

•MTX in lipid core nanoparticles (LDE) shows low toxicity and reduces inflammation.•LDE-MTX treatment reduces microglial activation and macrophage count in rats.•LDE-MTX boosts neuroprotection, increasing neuronal survival by 319 %.•LDE-MTX reduces ischemic stroke damage in rat models.•Potential novel treatment for ischemic stroke patients.

MTX in lipid core nanoparticles (LDE) shows low toxicity and reduces inflammation.

LDE-MTX treatment reduces microglial activation and macrophage count in rats.

LDE-MTX boosts neuroprotection, increasing neuronal survival by 319 %.

LDE-MTX reduces ischemic stroke damage in rat models.

Potential novel treatment for ischemic stroke patients.

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.