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

  • Bang, Woo-Seok (Department of Neurosurgery, Kyungpook National University Hospital) ;
  • Kim, Kyoung-Tae (Department of Neurosurgery, Kyungpook National University Hospital) ;
  • Cho, Dae-Chul (Department of Neurosurgery, Kyungpook National University Hospital) ;
  • Kim, Hye-Jeong (Department of Neurosurgery, Kyungpook National University Hospital) ;
  • Sung, Joo-Kyung (Department of Neurosurgery, Kyungpook National University Hospital)
  • Received : 2013.03.19
  • Accepted : 2013.07.17
  • Published : 2013.07.28

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.

Keywords

References

  1. Balentine JD : Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest 39 : 236-253, 1978
  2. Balentine JD : Pathology of experimental spinal cord trauma. II. Ultrastructure of axons and myelin. Lab Invest 39 : 254-266, 1978
  3. Basso DM, Beattie MS, Bresnahan JC : Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139 : 244-256, 1996 https://doi.org/10.1006/exnr.1996.0098
  4. Brederlau A, Correia AS, Anisimov SV, Elmi M, Paul G, Roybon L, et al. : Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease : effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells 24 : 1433-1440, 2006 https://doi.org/10.1634/stemcells.2005-0393
  5. Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, et al. : Embryonic stem cell-derived glial precursors : a source of myelinating transplants. Science 285 : 754-756, 1999 https://doi.org/10.1126/science.285.5428.754
  6. Bug G, Gül H, Schwarz K, Pfeifer H, Kampfmann M, Zheng X, et al. : Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Res 65 : 2537-2541, 2005 https://doi.org/10.1158/0008-5472.CAN-04-3011
  7. Chen PS, Peng GS, Li G, Yang S, Wu X, Wang CC, et al. : Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry 11 : 1116-1125, 2006 https://doi.org/10.1038/sj.mp.4001893
  8. Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT : Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 32 : 591-601, 2009 https://doi.org/10.1016/j.tins.2009.06.002
  9. Dash PK, Orsi SA, Zhang M, Grill RJ, Pati S, Zhao J, et al. : Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. PLoS One 5 : e11383, 2010 https://doi.org/10.1371/journal.pone.0011383
  10. Feng HL, Leng Y, Ma CH, Zhang J, Ren M, Chuang DM : Combined lithium and valproate treatment delays disease onset, reduces neurologionic cal deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model. Neuroscience 155 : 567-572, 2008 https://doi.org/10.1016/j.neuroscience.2008.06.040
  11. Gage FH, Coates PW, Palmer TD, Kuhn HG, Fisher LJ, Suhonen JO, et al. : Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci U S A 92 : 11879-11883, 1995 https://doi.org/10.1073/pnas.92.25.11879
  12. Go HS, Kim KC, Choi CS, Jeon SJ, Kwon KJ, Han SH, et al. : Prenatal exposure to valproic acid increases the neural progenitor cell pool and induces macrocephaly in rat brain via a mechanism involving the GSK-$3{\beta}/{\beta}$-catenin pathway. Neuropharmacology 63 : 1028-1041, 2012 https://doi.org/10.1016/j.neuropharm.2012.07.028
  13. Gorio A, Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, Cichetti C, et al. : Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci U S A 99 : 9450-9455, 2002 https://doi.org/10.1073/pnas.142287899
  14. Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, et al. : Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A 101 : 18117-18122, 2004 https://doi.org/10.1073/pnas.0408258102
  15. Inoue T, Kawaguchi S, Kurisu K : Spontaneous regeneration of the pyramidal tract after transection in young rats. Neurosci Lett 247 : 151-154, 1998 https://doi.org/10.1016/S0304-3940(98)00297-3
  16. Iseda T, Nishio T, Kawaguchi S, Yamanoto M, Kawasaki T, Wakisaka S : Spontaneous regeneration of the corticospinal tract after transection in young rats : a key role of reactive astrocytes in making favorable and unfavorable conditions for regeneration. Neuroscience 126 : 365-374, 2004 https://doi.org/10.1016/j.neuroscience.2004.03.056
  17. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisén J : Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96 : 25-34, 1999 https://doi.org/10.1016/S0092-8674(00)80956-3
  18. Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, et al. : Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25 : 4694-4705, 2005 https://doi.org/10.1523/JNEUROSCI.0311-05.2005
  19. Kikukawa S, Kawaguchi S, Mizoguchi A, Ide C, Koshinaga M : Regeneration of dorsal column axons after spinal cord injury in young rats. Neurosci Lett 249 : 135-138, 1998 https://doi.org/10.1016/S0304-3940(98)00406-6
  20. Kim HJ, Rowe M, Ren M, Hong JS, Chen PS, Chuang DM : Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke : multiple mechanisms of action. J Pharmacol Exp Ther 321 : 892-901, 2007 https://doi.org/10.1124/jpet.107.120188
  21. Lee H, Shamy GA, Elkabetz Y, Schofield CM, Harrsion NL, Panagiotakos G, et al. : Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells 25 : 1931-1939, 2007 https://doi.org/10.1634/stemcells.2007-0097
  22. Lee HJ, Wu J, Chung J, Wrathall JR : SOX2 expression is upregulated in adult spinal cord after contusion injury in both oligodendrocyte lineage and ependymal cells. J Neurosci Res 91 : 196-210, 2013 https://doi.org/10.1002/jnr.23151
  23. Lee SM, Yune TY, Kim SJ, Park DW, Lee YK, Kim YC, et al. : Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma 20 : 1017-1027, 2003 https://doi.org/10.1089/089771503770195867
  24. Li S, Strittmatter SM : Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci 23 : 4219-4227, 2003
  25. Maurer MH, Bromme JO, Feldmann RE Jr, Jarve A, Sabouri F, Bürgers HF, et al. : Glycogen synthase kinase 3beta (GSK3beta) regulates differentiation and proliferation in neural stem cells from the rat subventricular zone. J Proteome Res 6 : 1198-1208, 2007 https://doi.org/10.1021/pr0605825
  26. Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS : Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49 : 385-396, 2005 https://doi.org/10.1002/glia.20127
  27. Qing H, He G, Ly PT, Fox CJ, Staufenbiel M, Cai F, et al. : Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models. J Exp Med 205 : 2781-2789, 2008 https://doi.org/10.1084/jem.20081588
  28. Ren M, Leng Y, Jeong M, Leeds PR, Chuang DM : Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats : potential roles of histone deacetylase inhibition and heat shock protein induction. J Neurochem 89 : 1358-1367, 2004 https://doi.org/10.1111/j.1471-4159.2004.02406.x
  29. Rowland JW, Hawryluk GW, Kwon B, Fehlings MG : Current status of acute spinal cord injury pathophysiology and emerging therapies : promise on the horizon. Neurosurg Focus 25 : E2, 2008.
  30. Shibuya S, Miyamoto O, Auer RN, Itano T, Mori S, Norimatsu H : Embryonic intermediate filament, nestin, expression following traumatic spinal cord injury in adult rats. Neuroscience 114 : 905-916, 2002 https://doi.org/10.1016/S0306-4522(02)00323-8
  31. Sinn DI, Kim SJ, Chu K, Jung KH, Lee ST, Song EC, et al. : Valproic acid-mediated neuroprotection in intracerebral hemorrhage via histone deacetylase inhibition and transcriptional activation. Neurobiol Dis 26 : 464-472, 2007 https://doi.org/10.1016/j.nbd.2007.02.006
  32. Sugai F, Yamamoto Y, Miyaguchi K, Zhou Z, Sumi H, Hamasaki T, et al. : Benefit of valproic acid in suppressing disease progression of ALS model mice. Eur J Neurosci 20 : 3179-3183, 2004 https://doi.org/10.1111/j.1460-9568.2004.03765.x
  33. Sumner CJ, Huynh TN, Markowitz JA, Perhac JS, Hill B, Coovert DD, et al. : Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Ann Neurol 54 : 647-654, 2003 https://doi.org/10.1002/ana.10743
  34. Wang Z, Leng Y, Tsai LK, Leeds P, Chuang DM : Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia : the roles of HDAC and MMP-9 inhibition. J Cereb Blood Flow Metab 31 : 52-57, 2011 https://doi.org/10.1038/jcbfm.2010.195
  35. Yu SH, Cho DC, Kim KT, Nam KH, Cho HJ, Sung JK : The neuroprotective effect of treatment of valproic Acid in acute spinal cord injury. J Korean Neurosurg Soc 51 : 191-198, 2012 https://doi.org/10.3340/jkns.2012.51.4.191

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