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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bambakidis, Nicholas C. Horn, Eric M. 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.
Description	Country affiliation: United States Author Affiliation: Bambakidis NC ( Department of Neurological Surgery, Case Western Reserve University School of Medicine, and Neurological Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.)
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.
File Format	HTM / HTML
ISSN	15475654
Issue Number	2
Volume Number	10
e-ISSN	15475646
Journal	Journal of Neurosurgery: Spine
Language	English
Publisher	American Association of Neurological Surgeons
Publisher Date	2009-02-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Neurosurgery Contusions Pathology Therapy Hedgehog Proteins Agonists Spinal Cord Injuries Stem Cells Drug Effects Animals Cell Proliferation Metabolism Administration & Dosage Injections, Intraperitoneal Injections, Intravenous Intermediate Filament Proteins Kruppel-like Transcription Factors Nerve Tissue Proteins Nestin Rats Rats, Sprague-dawley Physiology Thoracic Vertebrae Journal Article
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical) Surgery

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