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.

Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature

“…Once again, corresponding constrictions have been observed in pial arteries (407,421,512), and reduced CBV by MRI, nearinfrared spectroscopy, multispectral reflectance, and intravascular dye imaging (18,71,195,227,351,407).…”

“…Corresponding changes in vessel diameter have been detected by intravital microscopy of pial arteries (16,46,54,59,359,419,420). Moreover, several surface reflectance and light transmission studies have detected reduced CBV preceding the hyperemia (FIGURE 5A; component I), or notched or jittery upstroke, in multiple species including rats and cats (98,163,227,299,303,305,306,359,407,442,444,474,479,481). Indeed, dramatic capillary red blood cell slowing, flow arrest, and even transient disappearance of red blood cells from capillary segments have all been observed (FIGURE 5B; component I), lasting as long as a minute during SD, without any evidence for focal or diffuse capillary narrowing or constriction, compression or collapse, or occlusion (59,479,480,490,491,532).…”

“…Direct pial artery diameter measurements showed a corresponding dilation (25-120%) in most studies, which appeared to be more prominent in smaller caliber arterioles than larger ones (16, 38, 46, 59, 64, 65, 314, 315, 407, 419 -422, 439, 460, 461, 512, 513). Multispectral reflectance, near-infrared spectroscopy, light transmission, and intravascular fluorescence imaging studies also showed hyperemia during SD in rats and cats (FIG-URE 5A; component II) (18,81,163,195,227,351,407,474,528). Hyperemia was further confirmed by magnetic resonance imaging (MRI), where CBV increased by ϳ30% for 1-2 min with a latency of 15-20 s after the apparent diffusion coefficient (ADC) changes during the depolarization (71).…”

“…This can be achieved chemically by direct application of depolarizing substances, such as concentrated KCl, glutamate receptor agonists particularly of NMDA subtype (496), and Ca 2ϩ or Na ϩ channel openers (e.g., BAY K 8644, aconitine); electrically by direct cathodal stimulation of tissue; and by mechanical stimulation (e.g., pinprick, focused ultrasound or laser) (230,381,407).…”

Multispectral imaging of absorption and scattering properties ofin vivoexposed rat brain using a digital red-green-blue camera

“…The average values of StO 2 during normoxia over all five samples were 47.49 AE 14.42%, which is lower than the value of around 60% reported in the literature. 38,42 This may be due to the experimental conditions of the present study, such as the type of anesthetic used, the anesthetic depth, or uncontrolled body temperature. Figure 15 shows the time courses of coefficient a, exponent b, μ rapid drop in O 2 tension, which causes depletion of adenosine triphosphate (ATP).…”