Original experimental rat model of blast-induced mild traumatic brain injury: a pilot study

ABSTRACT

Objective

Diagnosing blast-induced mild traumatic brain injury (mTBI) is difficult due to minimal imaging findings. This study aimed to establish a rat model of behavioral abnormality caused by blast-induced mTBI and detect new findings for therapeutic intervention.

Methods

We used a bench-top blast wave generator with the blast wave exiting through a 20-mm I.D. nozzle aimed at the focused target. The blast wave was directed at the head of male Wistar rats under general anesthesia positioned prone 2.5 cm below the nozzle. Peak shock wave pressure was 646.2 ± 70.3 kPa.

Results

After blast injury, mTBI rats did not show the findings of brain hemorrhage or contusion macroscopically and on hematoxylin-eosin-stained frozen sections but did show anorexia and weight loss in the early post-injury phase. Behavioral experiments revealed short-term memory impairment at 2 weeks and depression-like behavior at 2 and 6 weeks. Diffusion-weighted ex vivo MRI showed high-intensity areas in layers of the bilateral hippocampus. Immunohistochemical analysis revealed accumulation of reactive microglia and GFAP-positive astrocytes in the same region and loss of NeuN-positive neurons in the hippocampal pyramidal cell layer.

Conclusions

This model can reflect the pathophysiology of blast-induced mTBI and could potentially be used to develop therapeutic interventions in the future.

KEYWORDS:

• Explosion
• shock wave
• chronic encephalopathy syndrome
• mild traumatic brain injury

Acknowledgments

The authors are very grateful to Yuji Kawano and Yuta Hattori (PHOENIX TECHNO Co., Ltd., Osaka, Japan) for building the bench-top blast apparatus and providing technical support for its adjustment.

Declaration of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

The datasets generated for this study are available on request to the corresponding author.

Additional information

Funding

This work was supported by JSPS KAKENHI Grant Number 18KT0005 and Grant Number 17K17050.