Mechanical disruption of the blood-brain barrier following experimental concussion

Johnson, V. E., Weber, M. T., Xiao, R., Cullen, D. K., Meaney, D. F., Stewart, W. and Smith, D. H. (2018) Mechanical disruption of the blood-brain barrier following experimental concussion. Acta Neuropathologica, 135(5), pp. 711-726. (doi:10.1007/s00401-018-1824-0) (PMID:29460006)

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Abstract

Although concussion is now recognized as a major health issue, its non-lethal nature has limited characterization of the underlying pathophysiology. In particular, potential neuropathological changes have typically been inferred from non-invasive techniques or post-mortem examinations of severe traumatic brain injury (TBI). Here, we used a swine model of head rotational acceleration based on human concussion to examine blood–brain barrier (BBB) integrity after injury in association with diffuse axonal injury and glial responses. We then determined the potential clinical relevance of the swine concussion findings through comparisons with pathological changes in human severe TBI, where post-mortem examinations are possible. At 6–72 h post-injury in swine, we observed multifocal disruption of the BBB, demonstrated by extravasation of serum proteins, fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal pathology. BBB disruption was observed in a stereotyped distribution consistent with biomechanical insult. Specifically, extravasated serum proteins were frequently observed at interfaces between regions of tissue with differing material properties, including the gray–white boundary, periventricular and subpial regions. In addition, there was substantial overlap of BBB disruption with regions of axonal pathology in the white matter. Acute perivascular cellular uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP-positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive). Parallel examination of human severe TBI revealed similar patterns of serum extravasation and glial uptake of serum proteins, but to a much greater extent than in the swine model, attributed to the higher injury severity. These data suggest that BBB disruption represents a new and important pathological feature of concussion.

Item Type:Articles
Additional Information:Research reported in this publication was supported by the Department of Defense Grant W81XWH-13-1-0052, and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award numbers R01NS092398, R01NS094003 and R01NS038104, and the Department of Veterans Afairs under Merit Review number I01RX001097.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stewart, Dr William
Authors: Johnson, V. E., Weber, M. T., Xiao, R., Cullen, D. K., Meaney, D. F., Stewart, W., and Smith, D. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Acta Neuropathologica
Publisher:Springer
ISSN:0001-6322
ISSN (Online):1432-0533
Published Online:19 February 2018
Copyright Holders:Copyright © 2018 Springer-Verlag GmbH Germany, part of Springer Nature
First Published:First published in Acta Neuropathologica 135(5): 711-726
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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