TY - JOUR
T1 - Erythropoietin protects the subventricular zone and inhibits reactive astrogliosis in kaolin-induced hydrocephalic rats
AU - Suryaningtyas, Wihasto
AU - Arifin, Muhammad
AU - Rantam, Fedik Abdul
AU - Bajamal, Abdul Hafid
AU - Dahlan, Yoes Prijatna
AU - Dewa Gede Ugrasena, I.
AU - Maliawan, Sri
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/3/4
Y1 - 2019/3/4
N2 - 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.
AB - 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.
KW - Erythropoietin
KW - Hydrocephalus
KW - Lipid peroxidation
KW - Microgliosis
KW - Reactive astrocyte
KW - Subventricular zone
UR - http://www.scopus.com/inward/record.url?scp=85060337867&partnerID=8YFLogxK
U2 - 10.1007/s00381-019-04063-w
DO - 10.1007/s00381-019-04063-w
M3 - Article
C2 - 30661113
AN - SCOPUS:85060337867
SN - 0256-7040
VL - 35
SP - 469
EP - 476
JO - Child's Nervous System
JF - Child's Nervous System
IS - 3
ER -