title: An in vitro paradigm for diabetic cerebral oedema and its therapy: a critical role for taurine and water channels.
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.
authors.affiliation: Centre for Hormone Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Rd., Parkville, VIC 3052, Australia.
authors.forename: Ildi H
authors.initials: IH
authors.lastname: Koves
authors.forename: Vincenzo C
authors.initials: VC
authors.lastname: Russo
authors.forename: Sandra
authors.initials: S
authors.lastname: Higgins
authors.forename: Avantika
authors.initials: A
authors.lastname: Mishra
authors.forename: James
authors.initials: J
authors.lastname: Pitt
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Cameron
authors.forename: George A
authors.initials: GA
authors.lastname: Werther
mesh_terms: D020346:Aquaporins / Q000502:physiology*; D001483:Base Sequence; D001929:Brain Edema / Q000150:complications / Q000503:physiopathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D048909:Diabetes Complications; D006801:Humans; D066298:In Vitro Techniques; D008928:Mitochondria / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013654:Taurine / Q000502:physiology*
chemical_list: D020346:Aquaporins; D017931:DNA Primers; D013654:Taurine