Behavioral and Histopathological Impairments Caused by Topical Exposure of the Rat Brain to Mild-Impulse Laser-Induced Shock Waves: Impulse Dependency

Abstract

Although an enormous number of animal studies on blast-induced traumatic brain injury (bTBI) have been conducted, there still remain many uncertain issues in its neuropathology and mechanisms. This is partially due to the complex and hence difficult experimental environment settings, e.g., to minimize the effects of blast winds (tertiary mechanism) and to separate the effects of brain exposure and torso exposure. Since a laser-induced shock wave (LISW) is free from dynamic pressure and its energy is spatially well confined, the effects of pure shock wave exposure (primary mechanism) solely on the brain can be examined by using an LISW. In this study, we applied a set of four LISWs in the impulse range of 15–71 Pa·s to the rat brain through the intact scalp and skull; the interval between each exposure was ~5 s. For the rats, we conducted locomotor activity, elevated plus maze and forced swimming tests. Axonal injury in the brain was also examined by histological analysis using Bodian silver staining. Only the rats with exposure at higher impulses of 54 and 71 Pa·s showed significantly lower spontaneous movements at 1 and 2 days post-exposure by the locomotor activity test, but after 3 days post-exposure, they had recovered. At 7 days post-exposure, however, these rats (54 and 71 Pa·s) showed significantly higher levels of anxiety-related and depression-like behaviors by the elevated plus maze test and forced swimming test, respectively. To the best of the authors' knowledge, there have been few studies in which a rat model showed both anxiety-related and depression-like behaviors caused by blast or shock wave exposure. At that time point (7 days post-exposure), histological analysis showed significant decreases in axonal density in the cingulum bundle and corpus callosum in impulse-dependent manners; axons in the cingulum bundle were found to be more affected by a shock wave. Correlation analysis showed a statistically significant correlation between the depression like-behavior and axonal density reduction in the cingulum bundle. The results demonstrated the dependence of behavior deficits and axonal injury on the shock wave impulse loaded on the brain.

The cause of acute lethality of mice exposed to a laser-induced shock wave to the brainstem

“…The size of the mouse brain is roughly one-twentieth of that of the human brain 39 . On the basis of the scaling law, we believed that the appropriate shock wave duration to be applied to the mouse brain would be one-twentieth of the aforementioned durations, ranging from 12.5 μs to several hundred microseconds 40 . In this study, experiments were conducted according to the hypothesis that the force product is the most important parameter in determining damage 37 .…”

In vivo imaging of nitric oxide in the male rat brain exposed to a shock wave

“…Accordingly, this study consisted of the following four groups: Group 1 (sham control, n = 6), Group 2 (NO imaging with LISW exposure, CSD+, n = 6), Group 3 (NO synthase inhibitor administration and NO imaging with LISW exposure, CSD+, n = 6), and Group 4 (NO imaging with LISW exposure, CSD‐, n = 6). The rats used in this study were all male rats ( n = 30) and no female rats were enrolled to maintain consistency with our previous studies (Jitsu et al, 2021; Kawauchi et al, 2019, 2022; Sato et al, 2014).…”

“…The rats used in this study were all male rats (n = 30) and no female rats were enrolled to maintain consistency with our previous studies (Jitsu et al, 2021;Kawauchi et al, 2019Kawauchi et al, , 2022Sato et al, 2014).…”

“…It would be crucial to examine the cause of these hemodynamic abnormalities to fully understand the mechanisms of bTBI. Since LISW is spatially well confined and not accompanied by dynamic pressure (jet), this model allows us to observe the effects of primary blast (the effects of a shock wave itself) locally, in a limited brain region (Jitsu et al, 2021;Kawauchi et al, 2019Kawauchi et al, , 2022Sato et al, 2014).…”

Visceral hypersensitivity induced by mild traumatic brain injury via the corticotropin‐releasing hormone receptor: An animal model

“…27 The effects of blast injuries on the brain have been examined in several animal models, including actual micro explosions, 31 shock tubes, 32 blast tubes, 33 air guns 34 and laser-induced shock waves (LISW). 35 Among them, LISW generates extremely localized energy that hardly spread to the whole body from an impact point, and we suppose that LISW is superior to other methods in terms of safety, simplicity, controllability, and repeatability. 27,36 Other groups in our institution recently revealed that rats suffering from bTBI induced by LISW eventually develop anxiety-related and depression-like behaviors.…”