title: Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury.
abstract: OBJECTIVE
  Inflammation, which is known to be detrimental to the neurologic outcome during the acute phase after an ischemic stroke, provides a potential target for preventive or therapeutic approach for spinal cord ischemia-reperfusion injury. Tetramethylpyrazine (TMP), a pure compound derived from Ligusticum chuanxiong, is widely used in the treatment of ischemic stroke. The present study aimed to gain a deeper insight into the mechanism underlying the anti-inflammatory effects of TMP on spinal cord ischemia-reperfusion injury.
  
  
  METHODS
  Spinal cord ischemia was induced in male Sprague-Dawley rats by balloon occlusion of the thoracic aorta. The experimental groups (n = 30 per group) included sham operation, control (receiving only normal saline), and TMP (30 mg/kg, 30 minutes before occlusion). Neurologic function was assessed by the Basso, Beattie, and Bresnahan (BBB) score at 1, 6, 12, 24, and 48 hours after reperfusion. Histologic changes were studied using Nissl staining. Infarct volume was analyzed using 2,3,5-triphenyltetrazolium chloride staining. Myeloperoxidase (MPO) activity was determined by using a rat MPO assay kit. Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-10 and nuclear factor (NF)-κB were examined with immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blotting.
  
  
  RESULTS
  Compared with the control group, the TMP group showed significantly improved neurologic outcome (P < .05), decreased infarct volume (42.3% vs 17.4%), and alleviated neutrophil infiltration (0.35 vs 0.18 U/g). TMP treatment reduced the expressions of proinflammatory cytokines TNF-α (28.62 vs 15.23 pg/mg protein) and IL-1β (13.62 vs 8.24 pg/mg protein), upregulated the expression of anti-inflammatory cytokine IL-10 (18.35 vs 31.26 pg/mg protein), and inhibited the activation of NF-κB (2.78 vs 1.22) in ischemic spinal cord.
  
  
  CONCLUSIONS
  Treatment with TMP exerted a neuroprotective effect against spinal cord ischemia-reperfusion injury. The anti-inflammatory effect was believed to be one of the contributing mechanisms.
authors: Department of Orthopedics, Second Affiliated Hospital of Medicine School of Xi'an Jiaotong University, Xi'an Shaanxi, China.
authors: Lihong
authors: L
authors: Fan
authors: Kunzheng
authors: K
authors: Wang
authors: Zhibin
authors: Z
authors: Shi
authors: Jun
authors: J
authors: Die
authors: Chunsheng
authors: C
authors: Wang
authors: Xiaoqian
authors: X
authors: Dang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase; C017953:tetramethylpyrazine