title: Real-time optical diagnosis of the rat brain exposed to a laser-induced shock wave: observation of spreading depolarization, vasoconstriction and hypoxemia-oligemia.
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.
authors.affiliation: Division of Biomedical Information Sciences, National Defense Medical College Research Institute, Tokorozawa, Saitama, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sato
authors.affiliation: Division of Biomedical Information Sciences, National Defense Medical College Research Institute, Tokorozawa, Saitama, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kawauchi
authors.affiliation: Graduate School of Bio-Application and Systems Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Okuda
authors.affiliation: Graduate School of Bio-Application and Systems Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nishidate
authors.affiliation: Division of Neurosurgery, Tokorozawa Central Hospital, Tokorozawa, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nawashiro
authors.affiliation: Department of Defense Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Gentaro
authors.initials: G
authors.lastname: Tsumatori
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D002545:Brain Ischemia / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D003198:Computer Simulation; D003199:Computer Systems; D013181:Cortical Spreading Depression; D004560:Electricity; D004569:Electroencephalography; D006454:Hemoglobins / Q000378:metabolism; D002534:Hypoxia, Brain / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D053685:Laser Therapy; D008027:Light; D009010:Monte Carlo Method; D061848:Optical Imaging / Q000379:methods*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D012542:Scattering, Radiation; D012815:Signal Processing, Computer-Assisted; D062211:Spatio-Temporal Analysis; D019265:Spectroscopy, Near-Infrared; D014661:Vasoconstriction
chemical_list: D006454:Hemoglobins; D010100:Oxygen