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Brain tissue stiffness is a sensitive marker for acidosis.

Published version
Peer-reviewed

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Authors

Holtzmann, Kathrin 
Gautier, Hélène OB 
Christ, Andreas F 
Guck, Jochen 
Káradóttir, Ragnhildur Thóra 

Abstract

BACKGROUND: Carbon dioxide overdose is frequently used to cull rodents for tissue harvesting. However, this treatment may lead to respiratory acidosis, which potentially could change the properties of the investigated tissue. NEW METHOD: Mechanical tissue properties often change in pathological conditions and may thus offer a sensitive generic readout for changes in biological tissues with clinical relevance. In this study, we performed force-indentation measurements with an atomic force microscope on acute cerebellar slices from adult rats to test if brain tissue undergoes changes following overexposure to CO2 compared to other methods of euthanasia. RESULTS: The pH significantly decreased in brain tissue of animals exposed to CO2. Concomitant with the drop in pH, cerebellar grey matter significantly stiffened. Tissue stiffening was reproduced by incubation of acute cerebellar slices in acidic medium. COMPARISON WITH EXISTING METHODS: Tissue stiffness provides an early, generic indicator for pathophysiological changes in the CNS. Atomic force microscopy offers unprecedented high spatial resolution to detect such changes. CONCLUSIONS: Our results indicate that the stiffness particularly of grey matter strongly correlates with changes of the pH in the cerebellum. Furthermore, the method of tissue harvesting and preparation may not only change tissue stiffness but very likely also other physiologically relevant parameters, highlighting the importance of appropriate sample preparation.

Description

Keywords

AFM, Acidosis, Carbon dioxide, Cerebellum, Mechanical properties, Tissue mechanics, Acidosis, Animals, Biomechanical Phenomena, Brain, Carbon Dioxide, Elasticity, Hydrogen-Ion Concentration, Microscopy, Atomic Force, Rats, Tissue Culture Techniques

Journal Title

J Neurosci Methods

Conference Name

Journal ISSN

0165-0270
1872-678X

Volume Title

271

Publisher

Elsevier BV
Sponsorship
Medical Research Council (G1100312)
Human Frontier Science Program (HFSP) (RGY0074/2013)
Medical Research Council (G0701476)
Medical Research Council (MC_PC_12009)
Wellcome Trust (091543/Z/10/Z)
We acknowledge financial support from the UK Engineering and Physical Sciences Research Council (NanoDTC studentship to KH, Basic Technology Program Grant to JG, CASE studentship with JPK to AC), the UK Medical Research Council (G0701476 to RTK and HOBG, Career Development Award to KF), the Wellcome Trust (091543/Z/10/Z to RTK), and the Human Frontier Science Program (Young Investigator Award to KF).