title: Panax notoginsenoside produces neuroprotective effects in rat model of acute spinal cord ischemia-reperfusion injury.
abstract: BACKGROUND
  Acute spinal cord ischemia-reperfusion injury (SCII) is associated with pathological changes, including inflammation, edema, and neuronal apoptosis. Panax notoginsenoside (PNS), an important traditional Chinese medicine, has shown a variety of beneficial effects, including homeostasis maintenance, anti-myocardial ischemia activities, and neuroprotective functions. However, whether it can produce neuroprotective effects in SCII and the underlying mechanisms remain largely elusive.
  
  
  OBJECTIVE
  In the present study, we investigated the effects of PNS on neurological and histopathological changes after SCII as well as the underlying mechanisms.
  
  
  METHODS
  Sixty-four adult rats were randomly assigned into one of the four groups: the sham group, the ischemic group, the PNS group, and the Methylprednisolone group. A rat model of SCII was adopted from a commonly used protocol that was initially proposed by Zivin. Neurological function was evaluated with the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Histopathological changes were examined with hematoxylin and eosin staining as well as Nissl staining. Immunohistochemistry and Western blot were conducted to compare the changes in tumor necrosis factor-α, interleukin-1β, interleukin-10, aquaporin-4 (AQP-4), member 6 of the TNF receptor superfamily (Fas), and Fas ligand (FasL) in the spinal cord. Finally, neuronal apoptosis was measured by electron microscopy.
  
  
  RESULTS
  The BBB scores of the PNS-treated injured animals were significantly increased. The gross histopathological examination showed restored neuronal morphology and increased number of neurons after the PNS treatment. The PNS treatment decreased SCII-induced up-regulation of cytokine levels. In addition, PNS suppressed the increased expression of AQP-4 after SCII, suggesting an anti-edema effect. Finally, PNS treatment inhibited injury-induced apoptosis and reduced the expression levels of apoptosis-related proteins, Fas and FasL, confirming its anti-apoptosis effects against SCII.
  
  
  CONCLUSIONS
  The current findings suggest that PNS produces robust neuroprotective effects in spinal cord ischemia-reperfusion injury, and this role may be mediated by its anti-inflammation, anti-edema, and anti-apoptosis actions.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ning
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dang
authors.forename: Chuanyi
authors.initials: C
authors.lastname: Bai
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Kunzheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051401:Aquaporin 4 / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004487:Edema / Q000517:prevention & control; D053222:Fas Ligand Protein / Q000378:metabolism; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D053723:Panax notoginseng; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D053222:Fas Ligand Protein; C491898:Fas protein, rat; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; C519374:Panax notoginseng extract; D019014:fas Receptor