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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.00799

Changes in posttraumatic brain edema in craniectomy-selective brain hypothermia model are associated with modulation of aquaporin-4 level.

 Jacek Szczygielski1, 2, 3, 4*,  Cosmin Glameanu3, 5,  Andreas Müller3, Markus Klotz6, Christoph Sippl1, 3,  Vanessa Hubertus1, 3, 7, Karl-Herbert Schäfer8, Angelika Mautes3, 5, Karsten Schwerdtfeger1, 3 and Joachim Oertel1, 3
  • 1Department of Neurosurgery, Universitätsklinikum des Saarlandes, Germany
  • 2Institute of Neuropathology, Universitätsklinikum des Saarlandes, Germany
  • 3Department of Diagnostic and Interventional Radiology, Universitätsklinikum des Saarlandes, Germany
  • 4Faculty of Medicine, University of Rzeszow, Poland
  • 5Department of Neurosurgery, Universitätsklinikum des Saarlandes, Germany
  • 6Research and Development Center - Germany, RAM Group, Germany
  • 7Department of Neurosurgery, Charité Universitätsmedizin Berlin, Germany
  • 8Campus Zweibrücken, Hochschule Kaiserslautern University of Applied Sciences, Germany

Both hypothermia and decompressive craniectomy have been considered as a treatment for traumatic brain injury. In previous experiments we established a murine model of decompressive craniectomy and we presented attenuated edema formation due to focal brain cooling. Since edema development is regulated via function of water channel proteins, our hypothesis was that the effects of decompressive craniectomy and of hypothermia are associated with a change in aquaporin-4 (AQP4) concentration.
Male CD-1 mice were assigned into following groups (n =5): sham, decompressive craniectomy, trauma, trauma followed by decompressive craniectomy and trauma + decompressive craniectomy followed by focal hypothermia. After 24h, magnetic resonance imaging with volumetric evaluation of edema and contusion were performed, followed by ELISA analysis of AQP4 concentration in brain homogenates. Additional histopathological analysis of AQP4 immunoreactivity has been performed at more remote time point of 28d.
Correlation analysis revealed a relationship between AQP4 level and both volume of edema (r2 = 0.45, p < 0.01, **) and contusion (r2 = 0.41, p < 0.01, **) 24h after injury.
Aggregated analysis of AQP4 level (mean ± SEM) presented increased AQP4 concentration in animals subjected to trauma and decompressive craniectomy (52.1 ± 5.2 pg/mL, p = 0.01; *), but not to trauma, decompressive craniectomy and hypothermia (45.3 ± 3.6 pg/mL, p > 0.05; ns) as compared with animals subjected to decompressive craniectomy only (32.8 ± 2.4 pg/mL). However, semiquantitative histopathological analysis at remote time point revealed no significant difference in AQP4 immunoreactivity across the experimental groups.
This suggests that AQP4 is involved in early stages of brain edema formation after surgical decompression. The protective effect of selective brain cooling may be related to change in AQP4 response after decompressive craniectomy. The therapeutic potential of this interaction should be further explored.

Keywords: Traumatic Brain Injury, Decompressive Craniectomy, Brain Edema, aquaporin-4 (AQP4), Hypothermia, mouse model

Received: 26 May 2018; Accepted: 04 Sep 2018.

Edited by:

Stefania Mondello, Università degli Studi di Messina, Italy

Reviewed by:

Endre Czeiter, University of Pécs, Hungary
Valentina Di Pietro, University of Birmingham, United Kingdom
Weiwei Zhong, Emory University, United States  

Copyright: © 2018 Szczygielski, Glameanu, Müller, Klotz, Sippl, Hubertus, Schäfer, Mautes, Schwerdtfeger and Oertel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD. Jacek Szczygielski, Universitätsklinikum des Saarlandes, Department of Neurosurgery, Geb. 90.5, Homburg, 66421, Germany, jacek.szczygielski@uks.eu