Child's Nervous System

, Volume 35, Issue 3, pp 469–476 | Cite as

Erythropoietin protects the subventricular zone and inhibits reactive astrogliosis in kaolin-induced hydrocephalic rats

  • Wihasto SuryaningtyasEmail author
  • Muhammad Arifin
  • Fedik Abdul Rantam
  • Abdul Hafid Bajamal
  • Yoes Prijatna Dahlan
  • I Dewa Gede Ugrasena
  • Sri Maliawan
Original Article



To elucidate the potential role of erythropoietin (EPO) as a neuroprotective agent against reactive astrogliosis and reducing the thinning rate of subventricular zone (SVZ) in kaolin-induced hydrocephalic rats.


Thirty-six ten-week-old Sprague-Dawley rats were used in this study. Hydrocephalus was induced with 20% kaolin suspension injected into the cistern of thirty rats and leaving the six rats as normal group. The hydrocephalic rats were randomly divided into hydrocephalic and treatment group. The treatment group received daily dose of recombinant human erythropoietin (rhEPO) from day 7 to day 21 after induction. The animals were sacrificed at 7 (only for hydrocephalic group) and 14 or 21 (for both groups) days after induction. Brain was removed and was prepared for histological analysis by hematoxylin and eosin staining as well as immunohistochemistry for 4-HNE, GFAP, Iba-1, and Ki-67.


Histopathological analysis showed that animals treated with rhEPO had a reduced astrocyte reactivity displayed by lower GFAP expression. Hydrocephalic rats received rhEPO also displayed reduced microglial activation shown by lower Iba-1 protein expression. Exogenous rhEPO exerted its protective action in reducing astrogliosis by inhibiting lipid peroxidation that was documented in this study as lower expression of 4-HNE than non-treated group. The SVZ thickness was progressively declining in hydrocephalus group, while the progression rate could be reduced by rhEPO.


Erythropoietin has a potential use for inhibiting lipid peroxidation, and reactive astrogliosis in hydrocephalic animal model. The reduced thinning rate of SVZ demonstrated that EPO also had effect in reducing the hydrocephalus progressivity. Further research is warranted to explore its efficacy and safety to use in clinical setting.


Erythropoietin Hydrocephalus Reactive astrocyte Microgliosis Subventricular zone Lipid peroxidation 



The authors would like to acknowledge Widjiati, D.V.M, Ph.D, and Dewita, D.V.M for helping in animal care. We also send gratitude to Hari Basuki Notobroto, M.D., Ph.D for statistical advice.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

Ethical approval

All procedures involving animals performed in this study were in accordance with the ethical standards of The Institutional Animal Care and Use Committee of Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, where the study was conducted.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryFaculty of Medicine Universitas Airlangga – Dr. Soetomo General HospitalSurabayaIndonesia
  2. 2.Department of Veterinary Microbiology - Faculty of Veterinary Medicine And Laboratory for Stem Cell Research - Institute of Tropical DiseaseUniversitas AirlanggaSurabayaIndonesia
  3. 3.Department of ParasitologyFaculty of Medicine Universitas AirlanggaSurabayaIndonesia
  4. 4.Department of Child HealthFaculty of Medicine Universitas Airlangga – Dr. Soetomo General HospitalSurabayaIndonesia
  5. 5.Department of NeurosurgeryFaculty of Medicine Universitas Udayana – Sanglah General HospitalDenpasarIndonesia

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