Intravenous Hedgehog Agonist Induces Proliferation Of Neural And Oligodendrocyte Precursors In Rodent Spinal Cord Injury

Authors

Nicholas C. BambakidisFollow
Xukui Wang
Ronald J. Lukas, Barrow Neurological InstituteFollow
Robert F. SpetzlerFollow
Volker K.H. SonntagFollow
Mark C. PreulFollow

Department

neurobiology

Document Type

Article

Abstract

BACKGROUND: Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor gli-1 and plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into adult rodent spinal cords after injury. OBJECTIVE: To use small-molecule agonists of the hedgehog pathway in an attempt to replicate these findings with intravenous administration. METHODS: Forty Sprague-Dawley rats were randomly divided into 4 groups. Saline treatment control groups were divided into a contusion injury group and a noninjury sham group; Shh agonist treatment groups were divided into an injury group and a noninjury sham group. Shh agonist Ag11.1 was administered to the treatment groups and saline to the control groups. Injections were performed on days 1 and 4 after surgery. On day 14, 1 group was sacrificed, and injured spinal cord portions were removed for explant cultures. After 7 days in culture, specimens were fixed for immunostaining neural precursor cells, and cell counts were taken. RESULTS: Histological analysis demonstrated cystic cavitary lesions with a rim of white-matter sparing in all specimens. In animals treated with hedgehog agonist for a contusion injury, a significant increase in the number of nestin- and musashi-1-positive neural precursor cells at the rim of the cavity was noted. CONCLUSION: There was a significant increase in the number of O4-positive oligodendrocyte precursors compared with uninjured controls and BrdU-positive cells, reproducing the findings of previous studies using direct Shh protein injection, which demonstrated spared white matter and increased recovery. © 2010 by the Congress of Neurological Surgeons.

Publication Date

12-1-2010

Publication Title

Neurosurgery

ISSN

0148396X

Volume

67

Issue

6

First Page

1709

Last Page

1715

Digital Object Identifier (DOI)

10.1227/NEU.0b013e3181f9b0a5

Recommended Citation

Bambakidis, Nicholas C.; Wang, Xukui; Lukas, Ronald J.; Spetzler, Robert F.; Sonntag, Volker K.H.; and Preul, Mark C., "Intravenous Hedgehog Agonist Induces Proliferation Of Neural And Oligodendrocyte Precursors In Rodent Spinal Cord Injury" (2010). Translational Neuroscience. 240.
https://scholar.barrowneuro.org/neurobiology/240