Effects of Embryonic Neural Stem Cell Therapy on DNA Damage Products in Urine and Tissue After Spinal Cord Injury in Rats


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ÖZGÖNÜL A. M. , KONYALIOĞLU S. , DAĞCI T. , KILINC E.

TURKIYE KLINIKLERI TIP BILIMLERI DERGISI, cilt.32, ss.1217-1225, 2012 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 32 Konu: 5
  • Basım Tarihi: 2012
  • Doi Numarası: 10.5336/medsci.2011-24284
  • Dergi Adı: TURKIYE KLINIKLERI TIP BILIMLERI DERGISI
  • Sayfa Sayıları: ss.1217-1225

Özet

Objective: We tested the hypothesis that embryonic neural stem cell (ENSC) therapy reduces neuronal DNA damage in the lesional spinal cord (SC) region and assessed the significance of some DNA breakdown products in urine and tissue samples as biomarkers of efficiency of the ENSC therapy. Material and Methods: DNA damage was measured by single cell gel electrophoresis (SCGE/Comet Assay) in spinal cord tissue of rats 7 (acute group) and 28 (chronic group) days after surgical resections of a 10 mm segment of the cord below T8-T9 and sham operations. As biomarkers of DNA damage, urinary 5-(hydroxymethyl) uracil (5HMU) and 2'-deoxyuridine (2dU) were analyzed by high-performance liquid chromatography (HPLC) with electrochemical detection (ED). Results: Comet scores of the lesioned tissues were significantly higher in the acute and chronic spinal cord injury (SCI) compared to the sham operated groups (p=0.009 and p=0.009, respectively). After the ENSC transplantation, tail %, tail length and tail moment (T%, TL and TM, respectively) decreased in acute (p=0.009, p=0.009 and p=0.009, respectively) and chronically (p=0.009, p=0.009, p=0.009 respectively) injured rats. 5HMU and 2dU were significantly higher in the acute and the chronic groups than in the sham operated groups (p=0.009 and p=0.009, respectively). 5HMU concentration in the acute SCI group had a stronger correlation strongly with tail moment (r=0.9039, p=0.02). In the chronic injury group, 5HMU and 2dU concentrations correlated significantly with tail length (r=0.9990, p=0.001 and r=0.9272, p=0.016, respectively). While 5HMU seems to be a better biomarker for acute injury, both HMU and 2dU excretions increase in chronic damage. Besides, neurological functions of all the study animals were measured with the Basso-Beattie-Bresnahan (BBB) score. Conclusion: Our results demonstrated that ENSC therapy of the lesioned tissue significantly decreased the levels of DNA breakdown products in urine and tissue samples of rats with acute and chronic SCI. Assessment of neurological recovery with the BBB test confirmed these findings.