Brain Redox Imaging Using In Vivo Electron Paramagnetic Resonance Imaging and Nitroxide Imaging Probes

Abstract

Reactive oxygen species (ROS) are produced by living organisms as a result of normal cellular metabolism. Under normal physiological conditions, oxidative damage is prevented by the regulation of ROS by the antioxidant network. However, increased ROS and decreased antioxidant defense may contribute to many brain disorders, such as stroke, Parkinson’s disease, and Alzheimer’s disease. Noninvasive assessment of brain redox status is necessary for monitoring the disease state and the oxidative damage. Continuous-wave electron paramagnetic resonance (CW-EPR) imaging using redox-sensitive imaging probes, such as nitroxides, is a powerful method for visualizing the redox status modulated by oxidative stress in vivo. For conventional CW-EPR imaging, however, poor signal-to-noise ratio, low acquisition efficiency, and lack of anatomic visualization limit its ability to achieve three-dimensional redox mapping of small rodent brains. In this review, we discuss the instrumentation and coregistration of EPR images to anatomical images and appropriate nitroxide imaging probes, all of which are needed for a sophisticated in vivo EPR imager for all rodents. Using new EPR imaging systems, site-specific distribution and kinetics of nitroxide imaging probes in rodent brains can be obtained more accurately, compared to previous EPR imaging systems. We also describe the redox imaging studies of animal models of brain disease using newly developed EPR imaging.

Development of an L‐band resonator optimized for fast scan EPR imaging of the mouse head

“…Systems have been developed to enable EPR imaging in living animals, and combination with MRI can provide anatomical registration of free radical distribution, 35,37 mapping functional parameters such as redox status, 1 oxygen tension, [38][39][40] pH, [41][42][43] distribution of glutathione, 4 and oxidative stress. 3 For these applications, it is essential to maximize both system sensitivity and stability.…”

“…Continuous wave (CW) EPR spectroscopy remains the most commonly used and versatile modality for biological EPR measurements because it is capable of detecting a wide range of EPR probes; spin trap adducts; and paramagnetic centers sampling critical properties of the in vivo biochemical microenvironment, including redox status, 1‐3 glutathione levels, 4 oxygen tension, 5,6 and pH 7,8 . Conventional CW‐EPR imaging uses typical commercial iron core electromagnets with Hall probe field controllers and is thus inherently slow, typically requiring seconds for each image projection, and minutes to even hours for high‐resolution spatial and spectral–spatial imaging 9‐11 .…”

Influence of a combination of triptolide and ferulic acid on the activities of CYP450 enzymes and oxidative stress in HaCaT cells

“…Therefore, these differences may help to explain why TP + FA did not exert significant effects on the three tested CYP450 enzymes in the present study. ROS are a metabolic signals produced under normal physiological conditions, and play essential roles in maintaining normal oxidative stress (39). The normal state of redox equilibrium is compromised when ROS levels exceed the capacity of the antioxidant defense system (40), which in turn interrupts cellular activities and induces apoptosis, tissue damage and aging (41,42).…”

Special Issue: Electron Paramagnetic Resonance

“…Recent achievements in both theory and instrumentation have made EPR central in order to study new interdisciplinary topics. Such achievements are found in the collection of papers from the Special Issue, devoted to EPR, with contributions in technical improvement [1,2], theory in physics [3], biology [2,4,5], and biochemistry [6]. This issue is articulated around three original articles and three specific reviews.…”

“…They presented a recent achievement, state of the art, as well as the limitations in the field. Finally, Hirotada Fujii and co-workers [2] presented a review of brain redox imaging using EPR and Nitroxide probe. They showed how EPR imaging could be used to study brain disorders like Parkinson's and Alzheimer's diseases.…”