Erythropoietin-mediated activation of aquaporin-4 channel for the treatment of experimental hydrocephalus

M. Rizwan Siddiqui, Furqan Attar, Vineet Mohanty, Kwang Sik Kim, C. Shekhar Mayanil, Tadanori Tomita*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Objective: In this study, we investigate a neuroprotective agent, erythropoietin (EPO), in animal hydrocephalus model and its potential reversal effects on hydrocephalus by altering the expression of aquaporin-4 (AQP4). Methods: Obstructive hydrocephalus was induced in 2-week-old rat pups by injecting kaolin (50 μl, 10 mg/ml in saline) into the cisterna magna, while the control pups received only saline. Kaolin-injected pups were divided into two groups on the fifth day after kaolin injection; one group received intra-peritoneal (i.p.) EPO (1 μg/pup) for 5 consecutive days, while other group received i.p. saline for 5 days. The effects of EPO on hydrocephalus were investigated by studying cerebral ventricle size and structural ependymal changes. We examined also the EPO effects on AQP4 expression and microRNA expression. Results: EPO treatment significantly reduced dilation of the cerebral ventricle and denudation of ependymal line in hydrocephalic pups comparing with the control group. Increased expression of AQP4 in periventricular ependymal lining and cultured astrocytes and increased vascular formation were noted after EPO treatment. Additionally, we identified miR-668 as an endogenous regulator of AQP4 in response to EPO. Anti-miR-668 dampened EPO-induced activation of AQP4 expression. Conclusions: Together, our results show that EPO-mediated upregulation of AQP4 significantly reduces dilation of the cerebral ventricles in obstructive hydrocephalus pups and may lead to potential therapeutic options for hydrocephalus.

Original languageEnglish (US)
Pages (from-to)2195-2202
Number of pages8
JournalChild's Nervous System
Volume34
Issue number11
DOIs
StatePublished - Nov 1 2018

Keywords

  • Aquaporin water channel
  • Erythropoietin
  • Hydrocephalus
  • MicroRNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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