J Korean Neurosurg Soc.  2013 Jul;54(1):8-13. 10.3340/jkns.2013.54.1.8.

Valproic Acid Increases Expression of Neuronal Stem/Progenitor Cell in Spinal Cord Injury

• Bang WS
• Kim KT
• Cho DC
• Kim HJ
• Sung JK

• KMID: 2190850
• DOI: http://doi.org/10.3340/jkns.2013.54.1.8

Abstract

OBJECTIVE
This study investigates the effect of valproic acid (VPA) on expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury (SCI) model.
METHODS
Adult male rats (n=24) were randomly and blindly allocated into three groups. Laminectomy at T9 was performed in all three groups. In group 1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received 1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing force of 30 grams was applied extradurally around the spinal cord at T9, and then rapidly released with cord compression persisting for 2 minutes. The rats were sacrificed and the spinal cord were collected one week after SCI. Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm rostral region to the lesion and prepared. We analyzed the nestin immunoreactivity from the white matter of ventral cord and the ependyma of central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by IHC and western blotting, respectively.
RESULTS
Nestin and SOX2 were expressed significantly in the SCI groups but not in the sham group. Comparing SCI groups, nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline group.
CONCLUSION
Nestin and SOX2 as markers for NSPCs showed increased expression in SCI-VPA group in comparison with SCI-saline group. This result suggests VPA increases expression of spinal NSPCs in SCI.

Keyword

Neural stem/progenitor cell; Spinal cord injury; Valproic acid; Nestin; SOX2

MeSH Terms

Aneurysm
Animals
Blotting, Western
Ependyma
Immunohistochemistry
Intermediate Filament Proteins
Laminectomy
Male
Nerve Tissue Proteins
Neurons
Rats
Spinal Cord
Spinal Cord Injuries
Valproic Acid
Intermediate Filament Proteins
Nerve Tissue Proteins
Valproic Acid

Figure

• 

  Fig. 1 Nestin expression in the white matter of spinal cord 1week after surgery at 5-mm rostral region to injury. A and D : Sham group-operated. B and E : SCI-saline group operated. C and F : SCI-VPA group operated. Scale bar=500 µm (A, B and C) and 50 µm (D, E and F). SCI : spinal cord injury, VPA : valproic acid.

• 

  Fig. 2 Density areas of nestin expression (µm2) in the white matter of ventral side in a cross section of spinal cord 1 week after surgery at 5-mm rostral region to injury (**p<0.05). SCI : spinal cord injury, VPA : valproic acid.

• 

  Fig. 3 Nestin expression in the ependyma of central canal 1 week after surgery at 5-mm rostral region to injury. A : Sham group-operated. B : SCI-saline group operated. C : SCI-VPA group operated. SCI : spinal cord injury, VPA : valproic acid.

• 

  Fig. 4 Density areas of nestin expression (µm2) in the ependyma of central canal 1 week after surgery at 5-mm rostral region to injury (**p<0.05). SCI : spinal cord injury, VPA : valproic acid.

• 

  Fig. 5 Western blot band of SOX2 and β-catenin. SCI : spinal cord injury, VPA : valproic acid.

• 

  Fig. 6 SOX2 protein levels relative to sham group (*p<0.1, **p<0.05).

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