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 laboratory mouse

EPR as a versatile and powerful tool in neurological diseases.

 

There are many arguments proving that oxidative stress is one of the indicators of epilepsy. It is also known that EPR imaging can be useful in monitoring oxidative stress. Thus, the question arises: is it possible to examine the kindling model of epilepsy by using a non-invasive method for obtaining redox data in order to reveal the sensitive oxidative damage in regions of the brain?

This question has been taken into consideration by a research group led by Emoto M.C.  The publication “Brain redox imagining in pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe” shows their approach to this matter.

A mouse kindling model of epilepsy (induced using PTZ) have been used in the experiment and it have been compared with the control group. With the help of EPR and the redox-sensitive imaging probe MCP, Emoto and colleagues could thoroughly observe changes of redox state in the brain of mice. They have obtained a three dimensional redox map that showed the difference between the brains of a PTZ-induced mouse and the control animals. The authors of this research concluded that during the epileptic seizures the hippocampus is highly vulnerable to damage caused by oxidative stress.

Studies also showed that no matter how many biomarkers of oxidative stress have been found, none of them is useful for examining and monitoring the effects of ROS in an animal model for a long period of time. EPR imaging with a nitroxide spin probe face up to these expectations allowing for visualizing and monitoring in vivo ROS under oxidative stress in real time.

This non-invasive method can be seen to be useful, not only with epileptic seizure models but also in other neurologic disorders such as  Alzheimer’s or Parkinson’s disease.

References:

Emoto MC, Yamata M, Sato-Akaba H, Yamada K,  Fujii HG; Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe; Neurosci Lett. 2015 Nov 3;608:40-4; DOI: 10.1016/j.neulet.2015.10.008.

 

injection to the mouse

It is possible to obtain 3D map of redox status in a fast and non-invasive way?

 

Antioxidant defence system and stabilized level of reactive oxygen species (ROS) protect organisms against various diseases such as stroke or inflammation. In order to create an effective therapy for such diseases, the in vivo redox status map may be useful. The fact is that EPR imaging, with a suitable external imaging probe, is a great tool for monitoring the balance or imbalance between oxidation and reduction reactions and assessing the redox state of the brain.

That issue was considered by Hirotada Fujii and his research group in the paper “Mapping of Redox Status in a Brain-Disease Mouse Model by Three-Dimensional EPR Imaging”.

Control mice and transient middle cerebral artery occlusion (MCAO) mice were used as the subjects in this experiment. The in vivo redox state in the brains of control and MCAO mice was measured by improved EPR imager that enabled rapid data acquisition, engineered by Fuji and colleagues. Reduction of the acquisition time has allowed to obtain high-quality 3D images in a very short time. A nitroxide, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxy (HMP), was used as a redox-sensitive spin probe. HMP has passed freely through the brain-blood barrier, which was also confirmed by MRI examination. 

The redox status of MCAO mice was visualized as 3D maps, where each voxel represents   half-live of HMP in the difference part of brain. The half-life mapping of HMP has shown a significant heterogeneity of the redox state in brain of MCAO mice. It was also revealed that there is an increase of HMP in the brain of ischemia-reperfusion-treated mice, and consequently, the reduction rate of nitroxide is slower in MCAO mice.

This study confirmed that with the use of an EPR scanner and given an appropriate time of data acquisition, is it possible to provide a 3D map of the in vivo redox state in the mouse brain . Therefore, the role of EPR imaging systems in the research on redox status is significant.

References:

Fujii H, Sato-Akaba H, Kawanishi K, Hirata H.; Mapping of redox status in a brain-disease mouse model by three-dimensional EPR imaging; Magn Reson Med. 2011 Jan;65(1):295-303; DOI: 10.1002/mrm.22598.

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The project is co-financed by the European Union from the European Regional Development Fund under the Smart Growth Operational Programme.
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The project is co-financed by the European Union from the European Regional Development Fund under the Smart Growth Operational Programme.