The pathobiology of blast injuries and blast-induced neurotrauma as identified using a new experimental model of injury in mice

被引:198
作者
Cernak, Ibolja [1 ]
Merkle, Andrew C. [1 ]
Koliatsos, Vassilis E. [2 ]
Bilik, Justin M. [1 ]
Luong, Quang T. [1 ]
Mahota, Theresa M. [1 ]
Xu, Leyan [2 ]
Slack, Nicole [1 ]
Windle, David [1 ]
Ahmed, Farid A. [1 ]
机构
[1] Johns Hopkins Univ, Biomed Business Area, Appl Phys Lab, Natl Secur Technol Dept, Laurel, MD 20723 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pathol, Laurel, MD 20723 USA
关键词
Blast; Blast injury; Traumatic brain injury; Blast-induced neurotrauma; Mouse; Behavior; Motor function; Cognitive function; PCR; Inflammation; TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; INFLAMMATORY RESPONSE; DELAYED EXPRESSION; GLIAL RESPONSES; REFERENCE GENES; PATHOLOGY; OSTEOPONTIN; STRESS; INVOLVEMENT;
D O I
10.1016/j.nbd.2010.10.025
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Current experimental models of blast injuries used to study blast-induced neurotrauma (BINT) vary widely, which makes the comparison of the experimental results extremely challenging. Most of the blast injury models replicate the ideal Friedlander type of blast wave, without the capability to generate blast signatures with multiple shock fronts and refraction waves as seen in real-life conditions; this significantly reduces their clinical and military relevance. Here, we describe the pathophysiological consequences of graded blast injuries and BINT generated by a newly developed, highly controlled, and reproducible model using a modular, multi-chamber shock tube capable of tailoring pressure wave signatures and reproducing complex shock wave signatures seen in theater. While functional deficits due to blast exposure represent the principal health problem for today's warfighters, the majority of available blast models induces tissue destruction rather than mimic functional deficits. Thus, the main goal of our model is to reliably reproduce long-term neurological impairments caused by blast. Physiological parameters, functional (motor, cognitive, and behavioral) outcomes, and underlying molecular mechanisms involved in inflammation measured in the brain over the 30 day post-blast period showed this model is capable of reproducing major neurological changes of clinical BINT. (c) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:538 / 551
页数:14
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