Novel Free Radical Monitoring in Patients with Neurological Emergency Diseases

Recent experimental studies have demonstrated that oxidative stress has important roles in various neuronal conditions. Stroke and traumatic brain injury are also related to oxidative stress. However few studies prove the existence of free radicals in hum

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Abstract  Recent experimental studies have demonstrated that oxidative stress has important roles in various neuronal conditions. Stroke and traumatic brain injury are also related to oxidative stress. However few studies prove the existence of free radicals in humans because they are difficult to measure. We recently developed a technique for free radical and oxidative stress monitoring using the ex vivo electron spin resonance (ESR) spin trapping method in patients with neuroemergency. Blood samples were collected by cathe-terization of the internal jugular bulb. The alkoxyl radical level was measured by ex vivo ESR spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (Dojin Chemical, Tokyo, Japan) as a spin trap. Electron spin response detection of the spin adduct was performed at room temperature using a JESREIX X-band spectrometer (JEOL, Tokyo, Japan). As a marker of reactive oxygen species, we also used the diacron-reactive oxygen metabolites test (d-ROM). This method is not invasive for patients, and it is technically easy to execute. Oxidative stress monitoring is useful and may prove valuable for clarifying the pathophysiology of neuroemergency diseases, which has long been hampered by technical difficulties in measuring and monitoring oxidative stress. Keywords  Head injury • free radical • oxidative stress • human • alkoxyl radical • monitoring • brain hypothermia • d-ROM test

Introduction Reactive oxygen species (ROS) have been shown to play an important role in various neuroemergencies and neurodegenerative diseases (1, 3–7, 9, 16, 18). Several lines of evidence support the contention that it is important to control free radical production in the treatment of many of these conditions (5, 6), even though their mechanistic effects are difficult to quantify. The pathophysiological steps in neuronal injury have gradually been clarified with the technical development of molecular biology. On the other hand, the brain is enriched with polyunsaturated fatty acids, rendering neuronal cells vulnerable to oxidative attack. In this regard, the control of radical formation has been shown to be very important for neuroprotection. In animal experiments, free radical scavengers and antioxidants have dramatically reduced cerebral damage (1–3, 5, 15, 20). However, clear corroboration of evidence from clinical studies has been somewhat slow in coming, and evidence obtained thus far is less than clear cut (10). Recently, we have developed the ex vivo electron spin resonance (ESR) spin trapping method for detecting free radicals in blood (5, 7, 8, 14). In this report, we introduce free radical monitoring using this method. We also describe another novel and simple oxidative stress monitoring technique using the diacron-reactive oxygen metabolites (d-ROM) test in patients with a neuroemergency.

Methods K. Dohi (*), and T. Aruga Department of Emergency and Critical Care Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan e-mail: [email protected] T. Nakamachi, H. Ohtaki and S. Yofu Depar