Neurotoxicity Research

, Volume 29, Issue 4, pp 514–524 | Cite as

Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats

  • Naser Amini
  • Nasim Vousooghi
  • Mahmoudreza Hadjighassem
  • Mehrdad Bakhtiyari
  • Neda Mousavi
  • Hosein Safakheil
  • leila Jafari
  • Arash Sarveazad
  • Abazar Yari
  • Sara Ramezani
  • Faezeh Faghihi
  • Mohammad Taghi JoghataeiEmail author
Original Article


Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.


Stem cell Kernicterus Phenyl hydrazine Sulfisoxazole 



The authors declare that they do not have any conflict of interests. This study was financially supported by the Grant No. 24317 from Iran University of Medical Sciences.

Compliance with Ethical Standards

Conflict of interest

No conflict of interest exists in the submission of this manuscript.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Naser Amini
    • 1
  • Nasim Vousooghi
    • 1
    • 2
  • Mahmoudreza Hadjighassem
    • 1
    • 3
  • Mehrdad Bakhtiyari
    • 4
  • Neda Mousavi
    • 5
  • Hosein Safakheil
    • 4
  • leila Jafari
    • 4
  • Arash Sarveazad
    • 6
  • Abazar Yari
    • 7
  • Sara Ramezani
    • 1
  • Faezeh Faghihi
    • 4
  • Mohammad Taghi Joghataei
    • 1
    • 4
    • 8
    Email author
  1. 1.Department of Neuroscience, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  2. 2.Iranian National Center for Addiction Studies (INCAS), Iranian Institute for Reduction of High-Risk BehaviorsTehran University of Medical SciencesTehranIran
  3. 3.Brain and Spinal Cord Injury Research CenterTehran University of Medical SciencesTehranIran
  4. 4.Cellular and Molecular Research CenterIran University of Medical SciencesTehranIran
  5. 5.Department of Cellular and Molecular NutritionTehran University of Medical SciencesTehranIran
  6. 6.Colorectal Research CenterIran University of Medical SciencesTehranIran
  7. 7.Department of AnatomyAlborz University of Medical SciencesKarajIran
  8. 8.Neuroscience Department, Faculty of Advanced Technologies in MedicineIran University of Medical SciencesTehranIran

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