PARP inhibition improves the effectiveness of neural stem cell transplantation in experimental brain trauma

  • Authors:
    • Zsombor Lacza
    • Eszter M. Horváth
    • Katalin Komjáti
    • Tibor Hortobágyi
    • Csaba Szabó
    • David W. Busija
  • View Affiliations

  • Published online on: August 1, 2003     https://doi.org/10.3892/ijmm.12.2.153
  • Pages: 153-159
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Abstract

Neural stem cell transplantation is a promising new treatment of ischemic or traumatic brain injury. We have now investigated the involvement of the peroxynitrite - poly(ADP-ribose) polymerase (ONOO− - PARP) activation cascade in brain trauma and neural stem cell transplantation. The forelimb motor cortex of adult male rats was exposed to cold lesion (−60°C) and motor function was monitored. Neural stem cells isolated from E14 rat embryos were labeled with brome deoxyuridine (BrDU) and injected into the injured cortex 6 days after the lesion. After another 6 days, the survival and differentiation of the grafted cells were investigated with immunohistochemistry. Increased production of ONOO− revealed by tyrosine nitration was seen in the lesion 2 days after transplantation. Animals treated with the ONOO− decomposition catalyst FP15 or the PARP inhibitor PJ34 had a significantly improved motor score, when compared to vehicle-treated controls. The neurological score further improved following stem cell grafting in the PJ34 treated, but not in the control animals. Six days after transplantation, differentiated BrDU positive cells were found in the cortical penumbra. The majority of these differentiated cells expressed an astrocyte marker and some of the cells expressed oligodendrocyte or neuronal markers. The number of surviving transplanted cells was significantly higher in the PJ34 treated group. Inhibition of the ONOO− - PARP activation cascade significantly improves the effectiveness of neural stem cell transplantation and promotes rapid functional recovery.

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August 2003
Volume 12 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lacza Z, Horváth EM, Komjáti K, Hortobágyi T, Szabó C and Busija DW: PARP inhibition improves the effectiveness of neural stem cell transplantation in experimental brain trauma. Int J Mol Med 12: 153-159, 2003
APA
Lacza, Z., Horváth, E.M., Komjáti, K., Hortobágyi, T., Szabó, C., & Busija, D.W. (2003). PARP inhibition improves the effectiveness of neural stem cell transplantation in experimental brain trauma. International Journal of Molecular Medicine, 12, 153-159. https://doi.org/10.3892/ijmm.12.2.153
MLA
Lacza, Z., Horváth, E. M., Komjáti, K., Hortobágyi, T., Szabó, C., Busija, D. W."PARP inhibition improves the effectiveness of neural stem cell transplantation in experimental brain trauma". International Journal of Molecular Medicine 12.2 (2003): 153-159.
Chicago
Lacza, Z., Horváth, E. M., Komjáti, K., Hortobágyi, T., Szabó, C., Busija, D. W."PARP inhibition improves the effectiveness of neural stem cell transplantation in experimental brain trauma". International Journal of Molecular Medicine 12, no. 2 (2003): 153-159. https://doi.org/10.3892/ijmm.12.2.153