title: Beneficial effects of early hemostasis on spinal cord injury in the rat.
abstract: METHODS
  Experimental study.
  
  
  OBJECTIVE
  To investigate the effect of early hemostasis on spinal cord injury (SCI).
  
  
  METHODS
  Fourth Military Medical University, Xi'an, China.
  
  
  METHODS
  Sprague Dawley rats were used. Hematoxylin and eosin (HE) staining was performed to observe hemorrhage at different time points (2, 6, 12, 24 and 48 h) after SCI to determine the time window of hemostatic drug administration (n=3 per time point). Three different concentrations of Etamsylate (0.025, 0.05 and 0.1 g kg-1) were administered immediately and 5 and 10 h after SCI to evaluate the effective dosage (n=6 per group). Another 82 rats were then randomly divided into two groups, Etamsylate group (0.1 g kg-1, n=41) and glucose control group (n=41). Nissl staining was performed to observe neurons at 10 days post injury. Immunohistochemistry, western blot and quantitative real-time PCR were performed to detect tissue necrosis at 7 d.p.i., the activation of astrocytes and microglia/macrophages and lesion cavity at 10 d.p.i. Basso-Beattie-Bresnahan scoring and rump height index assay were used to examine locomotion recovery.
  
  
  RESULTS
  Early hemostasis reduced the lesion area and tissue necrosis, enhanced neuronal survival, alleviated the activation of microglia/macrophages and astrocytes and facilitated functional recovery after spinal cord contusion in rats. Early hemostasis decreased hemorrhage area and lesion area after spinal cord transection in rats.
  
  
  CONCLUSIONS
  The present study demonstrated that early hemostasis has beneficial effects on SCI in the rat. It has the potential to be translated into clinical practice.
authors.affiliation: Institute of Neurosciences, Key Laboratory of Spinal Cord Injury and Repair, Fourth Military Medical University, Xi'an, China.
authors.forename: H
authors.initials: H
authors.lastname: Fan
authors.affiliation: Institute of Neurosciences, Key Laboratory of Spinal Cord Injury and Repair, Fourth Military Medical University, Xi'an, China.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.affiliation: Institute of Neurosciences, Key Laboratory of Spinal Cord Injury and Repair, Fourth Military Medical University, Xi'an, China.
authors.forename: L
authors.initials: L
authors.lastname: Duan
authors.affiliation: Institute of Neurosciences, Key Laboratory of Spinal Cord Injury and Repair, Fourth Military Medical University, Xi'an, China.
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Wang
authors.affiliation: Institute of Neurosciences, Key Laboratory of Spinal Cord Injury and Repair, Fourth Military Medical University, Xi'an, China.
authors.forename: G
authors.initials: G
authors.lastname: Ju
mesh_terms: D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004979:Ethamsylate / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D006490:Hemostatics; D008840:Microfilament Proteins; D004979:Ethamsylate; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat; D020930:MAP Kinase Kinase Kinases; C486651:Map3k9 protein, rat