title: Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.
abstract: OBJECTIVE
  Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration.
  
  
  METHODS
  The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted.
  
  
  RESULTS
  Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups.
  
  
  CONCLUSIONS
  An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.
authors.affiliation: Department of Neurological Surgery, Case Western Reserve University School of Medicine, and Neurological Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Bambakidis
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horn
authors.forename: Peter
authors.initials: P
authors.lastname: Nakaji
authors.forename: Nicholas
authors.initials: N
authors.lastname: Theodore
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bless
authors.forename: Tammy
authors.initials: T
authors.lastname: Dellovade
authors.forename: Chiyuan
authors.initials: C
authors.lastname: Ma
authors.forename: Xukui
authors.initials: X
authors.lastname: Wang
authors.forename: Mark C
authors.initials: MC
authors.lastname: Preul
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Coons
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spetzler
authors.forename: Volker K H
authors.initials: VK
authors.lastname: Sonntag
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003288:Contusions / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D053823:Hedgehog Proteins / Q000008:administration & dosage / Q000819:agonists*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013904:Thoracic Vertebrae; D000071676:Zinc Finger Protein GLI1
chemical_list: C498521:Gli1 protein, rat; D053823:Hedgehog Proteins; D007381:Intermediate Filament Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D000071676:Zinc Finger Protein GLI1