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Updated: May 4, 2026

Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics
Published on: November 30, 2012
Both water intoxication and osmotic BBB disruption increase brain water content in rats
P Kozler1, V Riljak, J Pokorný
1Institute of Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. pokorny@lf1.cuni.cz.
Abstract:
Our previous experiments revealed that water intoxication and osmotic BBB disruption in the rat allow penetration of high-molecular substances into the brain and that resulting changes in the internal environment of the CNS lead to pathological development, such as the loss of integrity of myelin. The aim of the present study was to determine whether the previously described phenomena are associated with increased water content in the brain. To answer the question following methods were used: a) water intoxication: intraperitoneal administration of distilled water, b) osmotic BBB disruption: application of mannitol (20 %) selectively into the internal carotid artery, c) brain wet weight was measured after decapitation, and subsequently (after six days in thermostat set at 86 °C) the dry weight were estimated d) in animals with 20 % and 30 % hyperhydration the degree of myelin deterioration was estimated e) animal locomotor activity was tested by continuous behavior tracking and analysis. Brain water content after water intoxication and following the administration of mannitol was higher than in the control group. Different degrees of hyperhydration led to different levels of brain water content and to different degrees of myelin impairment. Hyperhydration corresponding to 20 % of the body weight brought about lower locomotor activity. Increased water content in the brain after the BBB osmotic disruption is surprising because this method is frequently used in the clinical practice.
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