Laminarin attenuates cerebral ischemia-reperfusion injury by inhibiting Notch1 signaling and reprogramming microglial inflammatory responses
Dingzhi Chen, Jieqiong Xie, Xiaohui Wu, Deyan Kong, Jiefeng LuoBackground
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.
Methods
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.
Results
Laminarin reduced infarct volume and improved neurological recovery in rats. Bioinformatic analysis and immunofluorescence indicated involvement of the Notch pathway.
Conclusion
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.