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.

imaging of cortical vascular and hemodynamic responses to a shock wave: observation of spreading depolarization and oxygen supply-demand mismatch," J.Abstract. Blast-induced traumatic brain injury has been a recent major concern in neurotraumatology.However, its pathophysiology and mechanism are not understood partly due to insufficient information on the brain pathophysiology during/immediately after shock wave exposure. We transcranially applied a laserinduced shock wave (LISW, ∼19 Pa · s) to the left frontal region in a rat and performed multispectral imaging of the ipsilateral cortex through a cranial window (n ¼ 4). For the spectral data obtained, we conducted multiple regression analysis aided by Monte Carlo simulation to evaluate vascular diameters, regional hemoglobin concentration (rC Hb ), tissue oxygen saturation (StO 2 ), oxygen extraction fraction, and light-scattering signals as a signature of cortical spreading depolarization (CSD). Immediately after LISW exposure, rC Hb and StO 2 were significantly decreased with distinct venular constriction. CSD was then generated and was accompanied by distinct hyperemia/hyperoxemia. This was followed by oligemia with arteriolar constriction, but it soon recovered (within ∼20 min). However, severe hypoxemia was persistently observed during the post-CSD period (∼1 h). These observations indicate that inadequate oxygen supply and/or excessive oxygen consumption continued even after blood supply was restored in the cortex. Such a hypoxemic state and/or a hypermetabolic state might be associated with brain damage caused by a shock wave.

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Recently, terrorism using explosive devices has been increasing, resulting in a large number of patients suffering from blastinduced traumatic brain injury (bTBI). However, the pathophysiology and mechanism of bTBI are not well understood and thus, methods for diagnosis and treatment of bTBI have not yet been established. We applied a laser-induced shock wave (LISW) to the rat brain, for which various real-time diagnoses were performed. We observed spreading depolarization, longlasting vasoconstriction and hypoxemia-oligemia in the brain even under the LISW conditions causing no changes in systemic physiological parameters and limited hemorrhage and contusion in the cortex. Key words：Blast-induced traumatic brain injury, laser-induced shock wave, rat model, real-time diagnosis, spreading depolarization, long-lasting hypoxemia