Ultrastructural Brain Abnormalities and Associated Behavioral Changes in Mice After Low-Intensity Blast Exposure

Abstract

Explosive blast-induced mild traumatic brain injury (mTBI), a "signature wound" of recent military conflicts, commonly affects service members. While past blast injury studies have provided insights into TBI with moderate- to high-intensity explosions, the impact of primary low-intensity blast (LIB)-mediated pathobiology on neurological deficits requires further investigation. Our prior considerations of blast physics predicted ultrastructural injuries at nanoscale levels. Here, we provide quantitative data using a primary LIB injury murine model exposed to open field detonation of 350 g of high-energy explosive C4. We quantified ultrastructural and behavioral changes up to 30 days post blast injury (DPI). The use of an open-field experimental blast generated a primary blast wave with a peak overpressure of 6.76 PSI (46.6 kPa) at a 3-m distance from the center of the explosion, a positive phase duration of approximate 3.0 milliseconds (ms), a maximal impulse of 8.7 PSI x ms and a sharp rising time of 9 x 10-3 ms, with no apparent impact/acceleration in exposed animals. Neuropathologically, myelinated axonal damage was observed in blast-exposed groups at 7 DPI. Using transmission electron microscopy, we observed and quantified myelin sheath defects and mitochondrial abnormalities at 7 and 30 DPI. Inverse correlations between blast intensities and neurobehavioral outcomes including motor activities, anxiety levels, nesting behavior, spatial learning and memory occurred. These observations uncover unique ultrastructural brain abnormalities and associated behavioral changes due to primary blast injury and provide key insights into its pathogenesis and potential treatment.

Department(s)

Mining Engineering

Comments

The authors thank the technical support of Drs. Shanyan Chen and Zhe Qu for the initial blast studies. This publication was made possible by funding from the DoD Congressionally Directed Medical Research Programs (CDMRP) for the Peer Reviewed Alzheimer's Research Program Convergence Science Research Award (PRARP-CSRA; AZ140109) and the research funds of the University of Missouri (ZG) . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the United States government, the DoD, the United States Army or the Department of Veterans Affairs.

Keywords and Phrases

Animal cell; Animal experiment; Animal model; Animal tissue; Anxiety; Article; Behavior change; Blast injuries; Brain malformation; Controlled study; Explosion; Exposure; Male; Memory; Mitochondrion; Mouse; Myelin sheath; Nesting; Nonhuman; Open field behavior; Priority journal; Spatial learning; Transmission electron microscopy; Traumatic brain injury; Animal; Blast injury; Brain; Brain concussion; C57BL mouse; Disease model; Double blind procedure; Exploratory behavior; Immunohistochemistry; Maze test; Motor activity; Pathology; Psychology; Randomization; Recognition; Reversal learning; Spatial memory; Ultrastructure; Animals; Brain; Brain Concussion; Disease Models; Animal; Double-Blind Method; Exploratory Behavior; Immunohistochemistry; Male; Maze Learning; Mice; Inbred C57BL; Microscopy; Electron; Transmission; Mitochondria; Motor Activity; Myelin Sheath; Nesting Behavior; Random Allocation; Recognition (Psychology); Reversal Learning; Spatial Memory; Behavior; Blast wave; Blast-induced TBI; Neuropathology; Ultrastructural abnormalities

International Standard Serial Number (ISSN)

0166-4328

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2018 Elsevier, All rights reserved.

Publication Date

01 Jul 2018

PubMed ID

29526786

Link to Full Text

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