A low-intensity repetitive transcranial magnetic stimulation coupled to magnetic nanoparticles loaded with scutellarin enhances brain protection against cerebral ischemia reperfusion injury

It is reported here that a portable repetitive transcranial magnetic stimulation device with low intensity (LI-rTMS, 6–9 mT) combination with magnetic nanoparticles loaded with scutellarin (SCU MNPs), a flavone extracted from the Chinese herbal medicine Erigeron breviscapus (Vant.) Hand.-Mazz, can enhance the brain protection of SCU against cerebral ischemia/reperfusion (I/R) injury of rats. To establish the focal cerebral I/R injury model, the middle cerebral artery (MCA) of male Sprague-Dawley (SD) rats was occluded for 1 h. A prolonged blood circulation was observed in our SCU MNPs in rats with cerebral ischemia. More importantly, the accumulation of SCU in brain tissue caused by LI-rTMS during SCU MNPs treatment can significantly reduce the amount of cerebral infarct after cerebral I/R compared to free SCU or SCU MNPs alone. H&E and TUNEL staining also revealed that the combined use of SCU MNPs and LI-rTMS improved neuronal architecture and morphology, and reduced apoptosis in the brain, respectively. Results from SOD, MDA, TNF-α and IL-6 tests further confirm that LI-rTMS coupled with SCU MNPs can be synergistic in treating cerebral I/R injuries through anti-oxidant and anti-inflammatory pathways. As a result, our injectable SCU MNPs combined with LI-rTMS provide promising protection against brain damage caused by cerebral I/R, and the combination of magnetic nanoparticles with LI-rTMS may also be useful as a potential drug delivery system for brain diseases.