The Neurovascular Protective Effects of Huperzine A on D-Galactose-Induced Inflammatory Damage in the Rat Hippocampus

Background: Chronic administration of D-galactose (D-gal) results in oxidative stress and chronic inflammatory aging. Age-related changes in the brain result in neurovascular damage and blood-brain barrier (BBB) dysfunction. However, little is known regarding D-gal-induced neurovascular damage, as well as the protective effects of huperzine A. Objective: The purpose of this study was to utilize a D-gal-induced rat model to investigate the activation of neurovascular inflammatory damage and apoptosis in the rat hippocampus and to understand whether huperzine A alleviates D-gal-induced neuronal and vascular inflammatory injury. Methods: Aging rats were treated with D-gal (300 mg/kg s.c. for 8 weeks), were coadministered D-gal and huperzine A (D-gal 300 mg/kg and huperzine A 0.1 mg/kg s.c. for 8 weeks) or served as the saline-treated control group rats (same volume of saline given subcutaneously for 8 weeks). Changes in hippocampal morphology and biomarkers of inflammatory damage were analyzed. Results: Our study revealed that chronic administration of D-gal resulted in the activation of glia and vascular endothelial cells and upregulation of mRNA and protein levels of cell-associated adhesion molecules and inflammatory cytokines via nuclear factor (NF)-kappa B inhibitor degradation and NF-kappa B nuclear translocation. The inflammatory injury caused significant BBB dysfunction, decreased density of tight junctions (TJs) and apoptosis in the rat hippocampus. Coadministration of huperzine A not only markedly inhibited the D-gal-induced increase in acetylcholinesterase (AChE) activity, but also alleviated D-gal-induced neurovascular damage by inhibiting D-gal-induced NF-kappa B activation, improving cerebrovascular function and suppressing the D-gal-induced decrease in the density and protein levels of TJs and cell apoptosis. Conclusions: Our findings provided evidence that D-gal induced a proinflammatory phenotype mediated by NF-kappa B in the rat hippocampus. Moreover, huperzine A suppressed D-gal-induced neurovascular damage and BBB dysfunction, partly by preventing NF-kappa B nuclear translocation. The inhibiting effect of huperzine A on AChE activity might play an important role in attenuating D-gal-induced inflammatory damage. (C) 2014 S. Karger AG, Basel