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Thoracic shock wave injury causes behavioral abnormalities in mice

  • Experimental research - Brain Injury
  • Published:
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Abstract

Background

Mild traumatic brain injury (mTBI) is caused by complex mechanisms of systemic, local and cerebral responses to blast exposure. However, the molecular mechanisms of cognitive impairment after exposure to blast waves are not clearly known. We tested the hypothesis that thoracic injury induced functional and morphological impairment in the brain, leading to behavioral abnormalities.

Methods

Mice were exposed to laser-induced shock waves (LISWs) impacting the thorax and assessed for behavioral outcome at 7 and 28 days post injury. Hippocampus and lung were collected for histopathological analysis and gene expression profiling after injury.

Results

Thoracic injury transiently decreased the heart rate, blood pressure, peripheral oxyhemoglobin saturation and cerebral blood flow immediately after LISW exposure. Although LISWs exposure caused pulmonary contusions, hemorrhage was not apparent in the brain. At 7 and 28 days after, the injured mice exhibited impaired short-term memory and depression-like behavior compared with controls. Histological assessments showed an increase in neuronal cell death after shock wave exposure, especially in the CA3 region of the hippocampus. Moreover, shock wave exposure altered the expression of functionally relevant genes in the hippocampus at 1 h and 1 day post injury.

Conclusions

Our findings indicate that the LISW-induced thoracic injury with no direct impact on the brain affected the hippocampal gene expression and led to morphological alterations, resulting in behavioral abnormalities. Therefore, body protection may be extremely important in the effective prevention against blast-induced alterations in brain function.

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Acknowledgments

This study was supported by the Research Promotion Program for Defense Medicine from the National Defense Medical College (D.S.).

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Authors and Affiliations

  1. Division of Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Hiromi Miyazaki, Takami Saiki & Daizoh Saitoh

  2. Department of Traumatology and Critical Care Medicine, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Hiroki Miyawaki

  3. Department of Anesthesiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Yasushi Satoh

  4. Division of Biomedical Information Sciences, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Satoko Kawauchi & Shunichi Sato

Authors
  1. Hiromi Miyazaki
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  2. Hiroki Miyawaki
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  4. Takami Saiki
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  6. Shunichi Sato
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Correspondence to Hiromi Miyazaki.

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Comment

The study confirms that blast injury damages the brain by indirect multiple hit mechanisms principally involving the lungs.

As shown by others but not demonstrated here, the thoracic blast is most probably transmitted by the venous system intracranially as a pressure wave and produces cellular micro-lesions best observed in the CA3 region of the hippocampus. The authors show here that the thoracic blast induces a patho-physiological response resulting in a temporary brain hypoxia that added to the micro-mechanical injury results in delayed behavioural alterations that are mirrored by histopathological observations of delayed non-apoptotic neuronal necrosis mainly observed in the CA3 region. The authors also report acute changes in the gene expression profile of hippocampus neurones, further supporting the hypothesis that neurones respond to a metabolic stress.

Protecting the lungs saves the brain from blast injury!

Philippe Bijlenga

Geneva, Switzerland

Electronic supplementary material

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Fig. S1

Thoracic shock wave injury affects the hippocampal gene expression. The functional categories of the thoracic injury-regulated genes. The genes were categorized according to their biological function. Each bar represents the actual number of genes (PDF 101 kb)

Table S1

Genes upregulated in hippocampus at 1 h after shock wave exposure (PDF 11 kb)

Table S2

Genes downregulated in hippocampus at 1 h after shock wave exposure (PDF 5 kb)

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Miyazaki, H., Miyawaki, H., Satoh, Y. et al. Thoracic shock wave injury causes behavioral abnormalities in mice. Acta Neurochir 157, 2111–2120 (2015). https://doi.org/10.1007/s00701-015-2613-3

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  • DOI: https://doi.org/10.1007/s00701-015-2613-3

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