Experimental Animals
Online ISSN : 1881-7122
Print ISSN : 1341-1357
ISSN-L : 0007-5124
Original
A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics
Luca BordoniEugenio Gutiérrez JiménezSøren NielsenLeif ØstergaardSebastian Frische
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JOURNALS OPEN ACCESS

2020 Volume 69 Issue 1 Pages 92-103

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Abstract

The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg−1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.

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© 2020 Japanese Association for Laboratory Animal Science
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