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

作者：Koves Ildi H; Russo Vincenzo C; Higgins Sandra; Mishra Avantika; Pitt James; Cameron Fergus J; Werther George A^*

来源：Neurochemical Research, 2012, 37(1): 182-192.

DOI：10.1007/s11064-011-0598-8

• Diabetic ketoacidosis
• Children
• Cerebral oedema
• Idiogenic osmoles
• Taurine

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.

• 出版日期2012-1