Sonic hedgehog-induced neural precursor proliferation after adult rodent spinal cord injury.
OBJECTIVE
The glycoprotein molecule sonic hedgehog (Shh) has been shown to play a critical role in neuraxial development. To assess its role in the repair of demyelination following spinal cord injury (SCI), escalating doses of Shh were injected into demyelinated lesions in adult rat spinal cords.


METHODS
Twenty-seven adult rats underwent thoracic laminectomy and chemical demyelination of the spinal cord dorsal columns without neurological deficit A subset of 20 rats was treated after 3 days by direct injection of Shh at two different doses. Rats were killed at 7 or 21 days after SCI, and tissue samples underwent immediate fixation or were placed into cell culture. Diffuse cellular proliferative responses throughout the gray and white matter were observed in up to 70% of Shh-treated rats. Proliferation around the central canal, believed to be derived from the ventricular ependyma consistent with neuronal stem cell induction, was demonstrated in up to 60% of the treated rats. No significant proliferation in these areas was detected in control rats. Dorsal areas of nestin-positive cells were also observed in 70% of rats treated with high doses of Shh, and these observations were reproduced in cell culture as well as in cultures of dorsal spinal cord explants. Cell counts revealed significant increases in the percentage of oligodendrocyte precursors and neurons in treated compared with control rats.


CONCLUSIONS
Exogenous Shh administration promotes nestin-positive cell proliferation after SCI in adult rodents. These cells are believed to be derived from neural precursor cells. The populations of oligodendrocyte precursors and neurons were likewise increased in Shh-treated rats, suggesting that these cells may be derived from neural stem cells.
Bambakidis
Nicholas C
NC
Department of Neurosurgery, Case Western Reserve University, Cleveland, Ohio, USA. nbamba@juno.com
Wang
Rui-Zhen
RZ
Franic
Linda
L
Miller
Robert H
RH
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003711:Demyelinating Diseases / Q000188:drug therapy*; D004627:Embryonic Induction / Q000187:drug effects*; D053823:Hedgehog Proteins; D015552:Injections, Intralesional; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D023421:Models, Animal; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013234:Stem Cells / Q000187:drug effects; D015534:Trans-Activators / Q000008:administration & dosage / Q000494:pharmacology*
D053823:Hedgehog Proteins; D008244:Lysophosphatidylcholines; D015534:Trans-Activators