Real-time optical diagnosis of the rat brain exposed to a laser-induced shock wave: observation of spreading depolarization, vasoconstriction and hypoxemia-oligemia.

Shunichi Sato,Wataru Okuda,Hiroshi Nawashiro,Izumi Nishidate,Gentaro Tsumatori,Satoko Kawauchi,Cesar V Borlongan

doi:10.1371/journal.pone.0082891

Abstract

Despite many efforts, the pathophysiology and mechanism of blast-induced traumatic brain injury (bTBI) have not yet been elucidated, partially due to the difficulty of real-time diagnosis and extremely complex factors determining the outcome. In this study, we topically applied a laser-induced shock wave (LISW) to the rat brain through the skull, for which real-time measurements of optical diffuse reflectance and electroencephalogram (EEG) were performed. Even under conditions showing no clear changes in systemic physiological parameters, the brain showed a drastic light scattering change accompanied by EEG suppression, which indicated the occurrence of spreading depression, long-lasting hypoxemia and signal change indicating mitochondrial energy impairment. Under the standard LISW conditions examined, hemorrhage and contusion were not apparent in the cortex. To investigate events associated with spreading depression, measurement of direct current (DC) potential, light scattering imaging and stereomicroscopic observation of blood vessels were also conducted for the brain. After LISW application, we observed a distinct negative shift in the DC potential, which temporally coincided with the transit of a light scattering wave, showing the occurrence of spreading depolarization and concomitant change in light scattering. Blood vessels in the brain surface initially showed vasodilatation for 3–4 min, which was followed by long-lasting vasoconstriction, corresponding to hypoxemia. Computer simulation based on the inverse Monte Carlo method showed that hemoglobin oxygen saturation declined to as low as ∼35% in the long-term hypoxemic phase. Overall, we found that topical application of a shock wave to the brain caused spreading depolarization/depression and prolonged severe hypoxemia-oligemia, which might lead to pathological conditions in the brain. Although further study is needed, our findings suggest that spreading depolarization/depression is one of the key events determining the outcome in bTBI. Furthermore, a rat exposed to an LISW(s) can be a reliable laboratory animal model for blast injury research.

Highlights

There are many risks for humans to encounter blast or shock waves in military, industrial and even natural environments
The light scattering change accompanied by EEG suppression indicated the occurrence of spreading depression, and we examined related events to confirm this
Summary and correlation of observations In this study, we performed real-time measurements of diffuse reflectance signals and EEG for the rat brain that was exposed to a laser-induced shock wave (LISW)

Summary

Introduction

There are many risks for humans to encounter blast or shock waves in military, industrial and even natural environments. Terrorism using explosive devices has been increasing in recent years, resulting in a large number of patients suffering from blast-induced traumatic brain injury (bTBI) [1,2,3]. Many of them show no evident abnormality by conventional imaging diagnoses, such as MRI and X-ray CT, but are troubled with higher order brain dysfunction as well as post-traumatic stress disorder (PTSD) in the chronic phase, which is called mild bTBI (mbTBI) [4,5,6,7]. Natural blast or shock waves are caused by volcanic eruptions, lightning and meteorites. The recent explosion of a meteorite in Chelyabinsk, Russia resulted in injuries to more than one thousand people [8], and the outcomes of their injuries are unpredictable. Comprehensive investigation is needed to establish methods for prevention, diagnosis and treatment of bTBI, for which experiments using animal models are needed

Methods

Results

Conclusion