Laminarin attenuates cerebral ischemia-reperfusion injury by inhibiting Notch1 signaling and reprogramming microglial inflammatory responses

Neuroinflammation contributes to cerebral ischemia-reperfusion injury, and microglial inflammatory responses are regulated in part by Notch signaling. This study investigated whether laminarin, a brown algae-derived β-glucan polysaccharide, protects against cerebral ischemia-reperfusion injury by modulating Notch1-dependent microglial responses.

A rat middle cerebral artery occlusion/reperfusion model was established, and laminarin was administered intraperitoneally at 10 mg/kg for seven consecutive days. Neurological deficits and infarct volume were assessed by modified neurological severity score and 2,3,5-triphenyltetrazolium chloride staining. Transcriptomic and bioinformatic analyses were used to identify laminarin-associated pathways. BV2 microglial cells were stimulated with lipopolysaccharide, and Jagged1 was used to reactivate Notch signaling. Inducible nitric oxide synthase (iNOS), Arginase 1 (Arg1), Notch pathway proteins, and inflammatory cytokines were examined by immunofluorescence, western blotting, and enzyme-linked immunosorbent assay.

Laminarin reduced infarct volume and improved neurological recovery in rats. Bioinformatic analysis and immunofluorescence indicated involvement of the Notch pathway. In vivo and in vitro, laminarin decreased iNOS-associated pro-inflammatory activation and increased Arg1-associated reparative responses, accompanied by reduced Notch1/Hes1/Hes5 activation. Jagged1 attenuated these effects and partially reversed laminarin-mediated changes in inflammatory markers and cytokine production.

Laminarin attenuates cerebral ischemia-reperfusion injury by reprogramming microglial inflammatory responses, at least partly through inhibition of the Notch1/Hes1/Hes5 signaling pathway. These findings support laminarin as a potential marine-derived immunomodulatory candidate for ischemic stroke research.