Child's Nervous System

, Volume 28, Issue 5, pp 729–737 | Cite as

Simultaneous folate intake may prevent advers effect of valproic acid on neurulating nervous system

  • Ahmet Sukru Umur
  • Mehmet Selcuki
  • Adem Bursali
  • Nurcan Umur
  • Burcu Kara
  • H. Seda Vatansever
  • Yusuf Kurtulus Duransoy
Original Paper



The aim of this study is to elucidate the preventive effect of folic acid (FA) on teratogenic effects of valporic acid (VA) in early stage chick embryos on neural tube development.

Materials and methods

One hundred and fifty specific pathogen–free (SPF) chick eggs were used to investigate the neurulation in five groups. Group A was the control group. Group B was injected 0.02 ml of saline (0.9% NaCl) and was used for sham group. VA (0.72 mg) in 0.02 ml saline was injected in Group C, and 0.342 mcg of FA in 0.02 ml NaCl were administered to the embryos in Group D. VA (0.72 mg) + 0.342 mcg of FA in 0.02 ml saline were administered simultaneously to the eggs in Group E. At the end of 72 h, all embryos were extracted from eggs and were fixed, and for histological analyses hematoxylin and eosine was used, for detection of apoptotic cells terminal deoxyribonucleotide transferase-mediated dUTP-X nick end labeling (TUNEL) was used and for distribution of P53, bcl-2 and caspase-3, caspase-6, caspase-8 and caspase-9 immunoperoxidase techniques were used.


While there were no neural tube defects in the embryos of groups A, B and D, eight embryos died in group C and there were 12 embryos with retarded embryological development. In contrast to that, no death was observed in group E, but only eight embryos were detected with maldevelopmental delay stage.


These results suggested that VA may induce apoptotic mechanisms but not through the p53 pathway. In addition, FA effectively prevents the teratogenic influence of VA on chick embryo at neurulation stages by stopping cascade of apoptosis before caspase 3 expression.


Neural tube defect Chick embryo Neurulation Valproic acid Folic acid 



This investigation was presented at the annual meeting of International Society for Pediatric Neurosurgery, Jeju/Korea, 2010.

Conflict of interest

The authors do not have conflict of interest either with chemical used for the investigation or with the companies that produce the chemical used.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ahmet Sukru Umur
    • 1
  • Mehmet Selcuki
    • 1
  • Adem Bursali
    • 1
  • Nurcan Umur
    • 2
  • Burcu Kara
    • 3
  • H. Seda Vatansever
    • 3
  • Yusuf Kurtulus Duransoy
    • 1
  1. 1.Faculty of Medicine, Department of NeurosurgeryCelal Bayar UniversityManisaTurkey
  2. 2.Vocational School of Health ServicesCelal Bayar UniversityManisaTurkey
  3. 3.Faculty of Medicine, Histology and Embryology DeptCelal Bayar UniversityManisaTurkey

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