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

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Abstract

Purpose

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.

Method

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.

Results

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.

Conclusion

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Neurosurgery, Faculty of Medicine Universitas Airlangga – Dr. Soetomo General Hospital, Gedung Pusat Diagnostik Terpadu (GDC) Lantai 5, RSUD Dr. Soetomo, Jl. Mayjen Prof Moestopo 6-8, Surabaya, Indonesia

    Wihasto Suryaningtyas, Muhammad Arifin & Abdul Hafid Bajamal

  2. Department of Veterinary Microbiology - Faculty of Veterinary Medicine And Laboratory for Stem Cell Research - Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia

    Fedik Abdul Rantam

  3. Department of Parasitology, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia

    Yoes Prijatna Dahlan

  4. Department of Child Health, Faculty of Medicine Universitas Airlangga – Dr. Soetomo General Hospital, Surabaya, Indonesia

    I Dewa Gede Ugrasena

  5. Department of Neurosurgery, Faculty of Medicine Universitas Udayana – Sanglah General Hospital, Denpasar, Indonesia

    Sri Maliawan

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  1. Wihasto Suryaningtyas
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  2. Muhammad Arifin
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Correspondence to Wihasto Suryaningtyas.

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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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Suryaningtyas, W., Arifin, M., Rantam, F.A. et al. Erythropoietin protects the subventricular zone and inhibits reactive astrogliosis in kaolin-induced hydrocephalic rats. Childs Nerv Syst 35, 469–476 (2019). https://doi.org/10.1007/s00381-019-04063-w

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