We hypothesized that generation of nitric oxide (NO) was associated with persistent hemodynamic abnormalities observed in the rat cortex exposed to a shock wave. To examine this speculation, we performed in vivo imaging of NO in the rat cortex exposed to a laser-induced shock wave (LISW). An NO sensitive fluoroprobe (DAF-2 DA) was applied to the cortical surface, and NO-originating fluorescence was observed under the stereoscopic fluorescence microscope. We observed that the fluorescence intensity in perivascular spaces as well as in parenchyma was drastically increased after LISW application. Intense fluorescence spots in the parenchyma probably indicate NO generation from neurons.
Due to the frequent attacks using improvised explosive devices (IEDs), the number of patients suffering from blast-induced traumatic brain injury (bTBI) has been growing. Although most of the patients have been diagnosed as having mild bTBI, many of them show higher brain dysfunction in the chronic phase. However, the mechanisms of bTBI are unclear, and methods of prevention, diagnosis and treatment have therefore not been established. In our previous study, we applied a laser-induced shock wave (LISW) to the rat brain, for which real-time measurements of cerebral hemodynamics were conducted based on diffuse reflectance spectroscopy. We found that LISW application caused spreading depolarization (SD) and transient hyperemia/hyperoxemia, which was followed by persistent oligemia/hypoxemia in the cortex. We hypothesized that nitric oxide (NO) may be involved in these abnormal hemodynamic changes. In this study, we investigated our hypotheses using an inhibitor of NO synthesis. We observed that by inhibiting NO synthesis with LNAME, transient hyperemia and persistent oligemia/hypoxemia were reduced, suggesting that NO generation is activated by shock wave exposure and causes the abnormal hemodynamic changes in the rat brain.
The pathophysiology and mechanism of primary blast-induced traumatic brain injury (bTBI) have not yet been elucidated. We previously observed the occurrence of spreading depolarization (SD) and transient hyperemia/hyperoxemia followed by persistent oligemia/hypoxemia in the cortex of the rat brain exposed to a laserinduced shock wave (LISW). However, the mechanism of such hemodynamic abnormalities is not clear. In this study, we investigated the involvement of nitric oxide (NO), which is known as an endothelium-derived relaxing factor (EDRF) and also as a substance associated with vasoconstriction. By the inhibition of NO synthesis, we found that the transient hyperemia/hyperoxemia immediately after LISW application was diminished and the level of persistent oligemia/hypoxemia was mitigated even when SD occurred. The results suggest that hemodynamic abnormalities caused by an LISW in the rat cortex was associated with an increased NO production and its vasodilatory/vasoconstrictory effects.
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