Interstitial ion homeostasis and acid-base balance are maintained in oedematous brain of mice with acute toxic liver failure

Publication date: Available online 14 May 2018Source: Neurochemistry InternationalAuthor(s): Marta Obara-Michlewska, Fengfei Ding, Mariusz Popek, Alexei Verkhratsky, Maiken Nedergaard, Magdalena Zielinska, Jan AlbrechtAbstractAcute toxic liver failure (ATLF) rapidly leads to brain oedema and neurological decline. We evaluated the ability of ATLF-affected brain to control the ionic composition and acid-base balance of the interstitial fluid. ATLF was induced in 10–12 weeks old male C57Bl mice by single intraperitoneal (i.p.) injection of 100 μg/g azoxymethane (AOM). Analyses were carried out in cerebral cortex of precomatous mice 20–24 h after AOM administration. Brain fluid status was evaluated by measuring apparent diffusion coefficient [ADC] using NMR spectroscopy, Evans Blue extravasation, and accumulation of an intracisternally-injected fluorescent tracer. Extracellular pH ([pH]e) and ([K+]e) were measured in situ with ion-sensitive microelectrodes. Cerebral cortical microdialysates were subjected to photometric analysis of extracellular potassium ([K+]e), sodium ([Na+]e) and luminometric assay of extracellular lactate ([Lac]e). Potassium transport in cerebral cortical slices was measured ex vivo as 86Rb uptake. Cerebral cortex of AOM-treated mice presented decreased ADC supporting the view that ATLF-induced brain oedema is primarily cytotoxic in nature. In addition, increased Evans blue extravasation indicated blood brain barrier leakage, and increased fluoresce...
Source: Neurochemistry International - Category: Neuroscience Source Type: research