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An In Vitro Paradigm for Diabetic Cerebral Oedema and its Therapy: A Critical Role for Taurine and Water Channels

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Abstract

The pathophysiology of cerebral oedema (CE) in diabetic ketoacidosis (DKA) remains enigmatic. We investigated the role of the idiogenic osmol taurine and aquaporin channels in an in vitro model, the SH-SY5Y neuroblastoma cell line, by sequentially mimicking DKA-like hyperglycemia/hypertonicity and hypotonic fluid therapy. Exposure to DKA-like hyperosmolarity led to shrinkage, while hypotonic fluid exposure led to cell swelling and impaired viability. Low sodium compensated in part for elevated glucose, pointing to a critical role for overall osmolality. Taurine, was synthesized and retained intracellularly during DKA-like hypertonicity, and released during hypotonicity, in part mitigating neuronal swelling. Metabolic labeling showed that the rate of taurine release was inadequate to fully prevent neuronal swelling during hypotonic fluid therapy following DKA-like hypertonicity. Under these conditions, Aquaporin4 & 9 channels were respectively down and up-regulated. Our study provides further novel insights into molecular mechanisms contributing to CE in DKA and its therapy.

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Acknowledgments

These studies were supported by a grant in aid from the Australasian Paediatric Endocrine Group (APEG) sponsored by Novo Nordisk to IHK, VCR, FJC and GAW. IHK was a recipient of a University of Melbourne Research Scholarship. We also wish to thank Miss Elena Andaloro, Centre for Hormone Research, Murdoch Childrens Research Institute, for her excellent technical assistance.

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Authors and Affiliations

  1. Centre for Hormone Research, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Rd., Parkville, VIC, 3052, Australia

    Ildi H. Koves, Vincenzo C. Russo, Sandra Higgins, Fergus J. Cameron & George A. Werther

  2. Department of Endocrinology and Diabetes, Royal Children’s Hospital, Parkville, VIC, Australia

    Ildi H. Koves, Fergus J. Cameron & George A. Werther

  3. Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, VIC, Australia

    Ildi H. Koves, Vincenzo C. Russo, Sandra Higgins, James Pitt, Fergus J. Cameron & George A. Werther

  4. Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia

    Avantika Mishra & James Pitt

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  1. Ildi H. Koves
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  2. Vincenzo C. Russo
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  3. Sandra Higgins
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  4. Avantika Mishra
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  7. George A. Werther
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Correspondence to George A. Werther.

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Koves, I.H., Russo, V.C., Higgins, S. et al. An In Vitro Paradigm for Diabetic Cerebral Oedema and its Therapy: A Critical Role for Taurine and Water Channels. Neurochem Res 37, 182–192 (2012). https://doi.org/10.1007/s11064-011-0598-8

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  • DOI: https://doi.org/10.1007/s11064-011-0598-8

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