Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord: Laboratory investigation

Nicholas C. Bambakidis, Eric Horn, Peter Nakaji, Nicholas Theodore, Elizabeth Bless, Tammy Dellovade, Chiyuan Ma, Xukui Wang, Mark C. Preul, Stephen W. Coons, Robert F. Spetzler, Volker K H Sonntag

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Object. 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.

Original languageEnglish
Pages (from-to)171-176
Number of pages6
JournalJournal of Neurosurgery: Spine
Volume10
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Hedgehogs
Contusions
Spinal Cord
Stem Cells
Cell Proliferation
Hedgehog Proteins
Spinal Cord Injuries
Intravenous Administration
Rodentia
Up-Regulation
Nestin
Fixatives
Wounds and Injuries
Glycoproteins
Transcription Factors
Injections
Population

Keywords

  • Rat
  • Sonic hedgehog
  • Spinal cord injury
  • Stem cell

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Neurology

Cite this

Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord : Laboratory investigation. / Bambakidis, Nicholas C.; Horn, Eric; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C.; Coons, Stephen W.; Spetzler, Robert F.; Sonntag, Volker K H.

In: Journal of Neurosurgery: Spine, Vol. 10, No. 2, 02.2009, p. 171-176.

Research output: Contribution to journalArticle

Bambakidis, NC, Horn, E, Nakaji, P, Theodore, N, Bless, E, Dellovade, T, Ma, C, Wang, X, Preul, MC, Coons, SW, Spetzler, RF & Sonntag, VKH 2009, 'Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord: Laboratory investigation', Journal of Neurosurgery: Spine, vol. 10, no. 2, pp. 171-176. https://doi.org/10.3171/2008.10.SPI08231
Bambakidis, Nicholas C. ; Horn, Eric ; Nakaji, Peter ; Theodore, Nicholas ; Bless, Elizabeth ; Dellovade, Tammy ; Ma, Chiyuan ; Wang, Xukui ; Preul, Mark C. ; Coons, Stephen W. ; Spetzler, Robert F. ; Sonntag, Volker K H. / Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord : Laboratory investigation. In: Journal of Neurosurgery: Spine. 2009 ; Vol. 10, No. 2. pp. 171-176.
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abstract = "Object. 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.",
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AU - Bless, Elizabeth

AU - Dellovade, Tammy

AU - Ma, Chiyuan

AU - Wang, Xukui

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AU - Sonntag, Volker K H

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N2 - Object. 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.

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KW - Rat

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