EPR Overview

EPR is making its way to clinical studies Nowadays neurodegenerative disease such as Parkinson and Alzheimer’s are well known from taking their tolls. It is worth noticing that the imbalance between antioxidants and reactive oxygen species leads to damage caused by oxidative stress, and the oxidative damage is known for having an impact on the development of these diseases. The use of non-invasive EPR scanners and blood-brain permeative nitroxides, e.g. HMP or MCP, may be very helpful in the monitoring of changes in redox status. The Japanese research group led by M.C Emoto, has carried out an examination of the distribution and time courses reduction of 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCP). Studies were presented in the paper “Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia”. The process of examination have consisted of several stages, which included the anatomical imaging of an animal by MRI, the injection of MCP and HMP into the mouse, and the non-invasive imaging of the brain by a 3D EPR tomograph. After the nitroxides were injected, the changes in redox state in brains of the mice were monitored. As a result, very significant conclusions have been reached. Co-registered imaging clearly pointed out the differences in localization of both nitroxides. HMP has been distributed uniformly in mouse head and, contrary to MCP, has not been accumulated within the brain. The difference has been also found in perfusion rate, for HMP seems to be slower. After the in vivo studies, the mice were euthanized in order to assess the effect of blood flow on the redox reaction. Without blood flow, the half-life of HMP was significantly longer, while the half-life of MCP did not change at all. Nevertheless, MCP seems to be reduced inside  the brain with no loss of MCP from the brain by washout. It has been previously reported that many hydrophilic and lipophilic nitroxide compounds provide significant physiological information while being used as imaging probes. Designing of the experiment and the selection of the appropriate nitroxide spin probe can provide unique biological information, but it needs to be done with caution due to the lack of information about details concerning the time-dependent distribution and in vivo pharmacokinetics for the examination of small animals. References: Emoto MC, Sato-Akaba, Hirata, Fujii HG; Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia; Free Radic Biol Med. 2014 Sep;74:222-8; DOI: 10.1016/j.freeradbiomed.2014.06.026.

The Bright Side of Electron Paramagnetic Resonance. Monitoring the balance between oxidants and anti-oxidants, which is defined as a redox status, may help with providing a more efficient treatment of tumours, but it may also allow for a better understanding of neurodegenerative diseases. The balance between oxidation and reduction plays a crucial role in the well-being of lives. Electron Paramagnetic Resonance is a unique and non-invasive imaging tool which is capable of detecting redox-sensitive probes which can map the redox environment of a tissue or a cell. A research group from the Ohio State University has collected the advantages and examples of the use of EPR imaging and presented them in a paper titled “Redox Mapping of Biological Samples Using EPR Imaging”. Oxidative stress has been found to be one of the indicators of many pathological changes such as malignancy or inflammation. The possibility of acquiring a redox map of the tumour, provided by EPR imaging, can lead to the development of more effective therapeutic strategies. The authors of the paper presented a few experiments that showed the potential of EPR imaging. In the first one, the process of creating a redox map using electron paramagnetic resonance was described. Then the authors presented examples of application of imaging redox status in malignant tissue versus a normal one, in radiation-induced fibrosarcoma. There is also an examination of the effect of UV exposure on skin redox status. In another studies, imaging of the redox state was used to estimate the in vivo intracerebral reducing ability of mature rats after neonatal hypoxic-ischemic brain injury and to show the ischemic regions in isolated rat’s hearts. The last example of the use of EPR imaging concerned the use of a nitroxide spin label to measure the oxidative stress in the brain with Alzheimer’s disease. It has been confirmed that EPR imaging has a wide range of applications and it is found to be helpful for the detection and the examination of not only oncological diseases, but also other pathological states in living organisms. References: Aditi C. Kulkarni, Anna Bratasz, Brian Rivera, Murali C. Krishna, Periannan Kuppusamy; Redox Mapping of Biological Samples Using EPR Imaging; Israel Journal of Chemistry (Online) 48(1):27 – 31; DOI: 10.1560/IJC.48.1.27.