Laminaria japonica polysaccharide mitigates acute neuroinflammation in cerebral ischemia-reperfusion injury through Csf3-modulated pathways.

INTRODUCTION

Microglial hyperactivation-driven neuroinflammation is a major driver of secondary brain injury following cerebral ischemia/reperfusion (I/R), yet effective therapies targeting this pathological process remain limited. Marine-derived sulfated polysaccharides have emerged as promising anti-inflammatory agents, but the therapeutic potential and mechanisms of Laminaria japonica polysaccharide (LJP) in cerebral I/R injury are poorly understood.

METHODS

LJP was isolated from Laminaria japonica and structurally characterized via high-performance gel permeation chromatography (HPGPC), Fourier-transform infrared (FT-IR) spectroscopy, and ion chromatography. Its neuroprotective effects were evaluated in a mouse model of transient middle cerebral artery occlusion (tMCAO), with assessments of infarct volume, neurological function, and neuroinflammatory markers. Cross-species transcriptomic analysis identified potential targets, which were validated through in vivo and in vitro functional assays (rescue experiments with recombinant Csf3 and neutralization assays with Csf3-specific antibodies).

RESULTS

Structural characterization confirmed LJP is enriched in fucose, galacturonic acid, glucuronic acid, and sulfate groups. In tMCAO mice, LJP administration reduced infarct volume, improved neurological function, and suppressed microglial pro-inflammatory polarization, accompanied by decreased levels of interleukin-1b (IL-1b), tumor necrosis factor-α (TNFα), and interleukin-6 (IL-6). Transcriptomic analysis identified granulocyte colony-stimulating factor (Csf3/G-CSF) as a potential LJP-regulated mediator. Recombinant Csf3 partially reversed LJP's protective effects, while Csf3-specific antibodies failed to enhance LJP's anti-inflammatory benefits, suggesting Csf3 as an important contributory mechanism.

DISCUSSION: These findings demonstrate that LJP mitigates acute neuroinflammation post-I/R at least partly through Csf3 suppression, highlighting its promise as a novel phytotherapeutic agent for ischemic stroke.