Journal Article

Recurrent intermittent hyponatremia: A new experimental model

San Felipe, Diego, Tejedor, Marta, Marco, Eva M., Martín-Sánchez, Beatriz, Desco, Manuel, Lázaro, Alberto, López-Gallardo, Meritxell, Martín-Palumbo, Giovanna, Alvarez-Sala Walther, Luis Antonio, Cussó, Lorena, González-Nicolás, María Ángeles, Calle, Daniel, Uzun, Baris

2026

Overview

It is assumed that natremia remains low throughout the duration of chronic hyponatremia, inducing symptoms. We explore Recurrent Intermittent Hyponatremia (RIH) to establish whether a few hours of hyponatremia per day are enough to induce significant water retention. A rat model of RIH was developed and compared to control animals. Electrolyte balance and central nervous system (CNS) (water content and cellular changes) were studied at baseline and after a water overload equivalent to 10% of the animal's body weight. Apparent diffusion coefficient (ADC) obtained through magnetic resonance was used to study changes in content and distribution of brain water. Immunohistochemistry techniques were used to study in the CNS astroglial cells through the glial fibrillary acidic-protein (GFAP) expression; as well as oligodendrocytes and the myelin sheath using the myelin basic protein (MBP) antibody. Blood and urine analysis were performed to assess water and electrolyte balance. In RIH, mild hyponatremia was induced, but recovered after 24h; this situation was repeated for 7 consecutive days. A lower ADC value in the whole brain compared to control animals suggested an increase in total brain water in this situation. An increase in GFAP expression in the gray matter (GM) was observed, while MBP's expression remained unchanged. The water overload on RIH induced hypotonic hyponatremia, progressively decreased ADC values in the whole brain (less pronounced than in controls), and increased GFAP and MBP's expression in the white matter (similar increase found in controls). RIH is a novel animal model that suggests there can be significant water retention after only a few hours of hyponatremia a day provided this situation is repeated over time. Such water retention translates into a greater brain water accumulation and astroglial activation in the GM.

• Publisher: Public Library of Science,PLOS,Public Library of Science (PLoS)
• Subject: Adaptation / Anesthesia / Animal models / Animals / Astrocytes / Astrocytes - metabolism / Biology and Life Sciences / Body weight / Brain / Brain - metabolism / Brain - pathology / Central nervous system / Clinical medicine / Diffusion coefficient / Disease Models, Animal / Electrolyte balance / Electrolytes / Electrolytic cells / Experiments / Glial fibrillary acidic protein / Glial Fibrillary Acidic Protein - metabolism / Health care / Hyponatremia / Hyponatremia - metabolism / Hyponatremia - pathology / Immunohistochemistry / Magnetic resonance / Magnetic Resonance Imaging / Male / Medicine and Health Sciences / Metabolism / Moisture content / Myelin / Myelin basic protein / Myelin Basic Protein - metabolism / Myelin proteins / Neurophysiology / Oligodendrocytes / Overloading / Proteins / Rats / Rats, Wistar / Recurrence / Research and Analysis Methods / Retention / Rodents / Sheaths / Sodium / Substantia alba / Substantia grisea / Urine / Water / Water content / Water-Electrolyte Balance