title: Tetramethylpyrazine Facilitates Functional Recovery after Spinal Cord Injury by Inhibiting MMP2, MMP9, and Vascular Endothelial Cell Apoptosis.
abstract: Spinal cord injury (SCI) is a major public health issue that leads to neurological dysfunctions and morbidities in patients. Tetramethylpyrazine (TMP) plays a neuroprotective role in SCI; however, the underlying mechanism has not been fully elucidated.
  
  
  
  In the present study, we aimed to investigate the mechanisms and therapeutic effects of TMP on SCI.
  
  
  
  A contusion SCI model was established that used a modified Allen's method. In the TMP group, TMP (200 mg/kg) was injected daily for 5 days post-injury, while in the Negative Control (NC) group, an equal volume of normal saline was injected. Hindlimb motor function was evaluated using the Basso, Beattie, Bresnahan (BBB) scale. The effects of TMP on protein levels of the matrix metalloproteinases 2 (MMP2) and 9 (MMP9), Bax and cleaved caspase-3 were determined by western blotting. Apoptotic changes in vascular endothelial cells were evaluated using immunofluorescence and TUNEL staining. Alterations in 3D vessel morphology after treatment with TMP were assessed by synchrotron radiation micro-CT (SRμCT).
  
  
  
  TMP treatment significantly improved recovery in hindlimb motor function and attenuated vascular endothelial cell apoptosis in rats with SCI. Additionally, TMP treatment markedly decreased the protein levels of MMP2 and MMP9, pro-apoptotic bax and cleaved caspase-3 while promoting angiogenesis, as evidenced by vessel visualization using SRμCT.
  
  
  
  These results indicate that TMP attenuated SCI-induced neurological impairments by the down-regulation of the expression of MMP2 and MMP9 proteins, the inhibition of vascular endothelial cell apoptosis, and the promotion of angiogenesis.
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Hu
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Xiao-Kai
authors.initials: XK
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Hunan, China.
authors.forename: Dong-Zhe
authors.initials: DZ
authors.lastname: Li
authors.affiliation: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Hunan, China.
authors.forename: Tian-Ding
authors.initials: TD
authors.lastname: Wu
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Da-Qi
authors.initials: DQ
authors.lastname: Xu
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, 2nd Surgical Building, Xiangya Hospital, Central South University, 87th Xiangya Street, Changsha, Hunan 410008, China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects*; D005500:Follow-Up Studies; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009460:Neurologic Examination; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C017953:tetramethylpyrazine
keywords: MMP2; MMP9; Tetramethylpyrazine; spinal cord injury; vascular endothelial cell apoptosis