title: The neurovascular protective effects of huperzine A on D-galactose-induced inflammatory damage in the rat hippocampus.
abstract: 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)-κB inhibitor degradation and NF-κB 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-κB 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-κB in the rat hippocampus. Moreover, huperzine A suppressed D-gal-induced neurovascular damage and BBB dysfunction, partly by preventing NF-κB nuclear translocation. The inhibiting effect of huperzine A on AChE activity might play an important role in attenuating D-gal-induced inflammatory damage.
authors: Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors: Qingwei
authors: Q
authors: Ruan
authors: Xiaona
authors: X
authors: Hu
authors: Huafei
authors: H
authors: Ao
authors: Haifeng
authors: H
authors: Ma
authors: Zhanjuan
authors: Z
authors: Gao
authors: Fang
authors: F
authors: Liu
authors: Deqiu
authors: D
authors: Kong
authors: Zhijun
authors: Z
authors: Bao
authors: Zhuowei
authors: Z
authors: Yu
mesh_terms: D000375:Aging / Q000473:pathology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004660:Encephalitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005690:Galactose / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D020672:I-kappa B Proteins / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D012717:Sesquiterpenes; C050426:huperzine A; D000072000:NF-KappaB Inhibitor alpha; D005690:Galactose