• Jonas Blixt, Mikael Svensson, Eli Gunnarson, and Michael Wanecek.
• Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: Jonas.blixt@karolinska.se.
• Brain Res. 2015 Jun 22; 1611: 18-28.

AbstractTraumatic brain injury (TBI) is a major contributor to mortality and morbidity. The pathophysiology involves development of brain edema. Therapeutic options are limited as the mechanisms are not fully understood. Changes in the function of the blood-brain barrier (BBB), as well as variations in aquaporin expression, have been proposed to be involved in the development of the edema but the contribution of each factor has not been fully elucidated. In order to evaluate these mechanisms, in a potential window of opportunity, the early dynamic response was studied using an animal model causing a moderate TBI. Sprague-Dawley rats were subjected to blunt controlled head trauma and followed for up to four days by magnetic-resonance-imaging, immunohistofluorescence, immunohistochemistry, and quantitative protein analysis. Non-traumatized animals served as controls. TBI resulted in a midline shift and a decrease in Apparent Diffusion Coefficient, indicating a hemispheric enlargement due to cytotoxic edema. The tight junction protein Zona Occludens-1 was decreased (-25%) and associated with an increased IgG permeability (+20%) in the perilesional brain tissue in accordance with a BBB breakdown. The total amount of AQP4 protein decreased (-20%). The disruption of the BBB lasted for 4 days while the impact on AQP4 levels disappeared between day 1 and 4. Our findings shows that blunt focal brain injury results in an early development of brain edema involving both cytotoxic and vasogenic components, a persistent BBB breakdown and a temporary decrease in AQP4, and indicates that both types of edemas and mechanisms should be targeted in TBI treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

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