Enhancing the effects of transcranial magnetic stimulation with intravenously injected magnetic nanoparticles.

Transcranial magnetic stimulation (TMS) is a non-invasive and clinically approved method for treating neurological disorders. However, the relatively weak intracranial electric current induced by TMS is an obvious inferiority which can only produce limited treatment effects in clinical application. The present study aimed to investigate the possibility of enhancing the effects of TMS with intravenously administrated magnetic nanoparticles. To facilitate crossing of the blood-brain barrier (BBB), the superparamagnetic iron oxide nanoparticles (SPIONs) were coated with carboxylated chitosan and poly(ethylene glycol). To aid the nanoparticles in crossing the BBB and targeting the predesigned brain regions, an external permanent magnet was attached to the foreheads of the rats before the intravenous administration of SPIONs. The electrophysiological tests showed that the maximum MEP amplitude recorded in an individual rat was significantly higher in the SPIONs + magnet group than in the saline group (5.78 ± 2.54 vs. 1.80 ± 1.55 mV, P = 0.015). In the M1 region, biochemical tests detected that the number density of c-fos positive cells in the SPIONs + magnet group was 3.44 fold that of the saline group. These results suggest that intravenously injected SPIONs can enhance the effects of TMS in treating neurological disorders.

[1]  M. Ceccanti,et al.  Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole , 2018, Brain Stimulation.

[2]  Xue-Qing Zhang,et al.  Drug Delivery to the Brain across the Blood-Brain Barrier Using Nanomaterials. , 2017, Small.

[3]  A. Bonci,et al.  Rehabilitating the addicted brain with transcranial magnetic stimulation , 2017, Nature Reviews Neuroscience.

[4]  Saad M Ahsan,et al.  Chitosan as biomaterial in drug delivery and tissue engineering. , 2017, International journal of biological macromolecules.

[5]  J. Cheon,et al.  Synergism of Nanomaterials with Physical Stimuli for Biology and Medicine. , 2017, Accounts of chemical research.

[6]  U. Ziemann Thirty years of transcranial magnetic stimulation: where do we stand? , 2017, Experimental Brain Research.

[7]  T. Han,et al.  Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain. , 2016, Journal of visualized experiments : JoVE.

[8]  J. Reynolds,et al.  Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies , 2016, Front. Neural Circuits.

[9]  Emiliano Santarnecchi,et al.  Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease. , 2016, Current Alzheimer research.

[10]  Raquel Ferreira,et al.  Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[11]  A. Kaushik,et al.  Getting into the brain: Potential of nanotechnology in the management of NeuroAIDS. , 2016, Advanced drug delivery reviews.

[12]  Yinping Huang,et al.  Superparamagnetic Iron Oxide Nanoparticles Modified with Tween 80 Pass through the Intact Blood-Brain Barrier in Rats under Magnetic Field. , 2016, ACS applied materials & interfaces.

[13]  Jonathan S. Dordick,et al.  Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism , 2016, Nature.

[14]  D. Yarnitsky,et al.  ‘Virtual lesion’ in pain research; a study on magnetic stimulation of the primary motor cortex , 2016, European journal of pain.

[15]  J. Z. Hilt,et al.  Magnetic nanoparticles and nanocomposites for remote controlled therapies. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[16]  V. Balan,et al.  Doxorubicin-loaded magnetic nanocapsules based on N-palmitoyl chitosan and magnetite: Synthesis and characterization , 2015 .

[17]  Patrick W. Goodwill,et al.  Magnetic Particle Imaging tracks the long-term fate of in vivo neural cell implants with high image contrast , 2015, Scientific Reports.

[18]  R. Turcu,et al.  Developing novel strategies for the functionalization of core–shell magnetic nanoparticles with folic acid derivatives , 2015 .

[19]  Á. Pascual-Leone,et al.  Functional Dopaminergic Neurons in Substantia Nigra are Required for Transcranial Magnetic Stimulation-Induced Motor Plasticity. , 2015, Cerebral cortex.

[20]  Polina Anikeeva,et al.  Wireless magnetothermal deep brain stimulation , 2015, Science.

[21]  Jun Wang,et al.  One-pot synthesis of water-soluble superparamagnetic iron oxide nanoparticles and their MRI contrast effects in the mouse brains. , 2015, Materials science & engineering. C, Materials for biological applications.

[22]  M. Mahmoudi,et al.  Significance of surface charge and shell material of superparamagnetic iron oxide nanoparticle (SPION) based core/shell nanoparticles on the composition of the protein corona. , 2015, Biomaterials science.

[23]  Yu Cheng,et al.  Multifunctional nanoparticles for brain tumor imaging and therapy. , 2014, Advanced drug delivery reviews.

[24]  Noureddine Abidi,et al.  Changes in the cell wall and cellulose content of developing cotton fibers investigated by FTIR spectroscopy. , 2014, Carbohydrate polymers.

[25]  D. Durand,et al.  Long‐lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation , 2013, The Journal of physiology.

[26]  Ling Ye,et al.  Transferrin-conjugated, fluorescein-loaded magnetic nanoparticles for targeted delivery across the blood–brain barrier , 2013, Journal of Materials Science: Materials in Medicine.

[27]  Sungho Jin,et al.  Magnetic targeting of nanoparticles across the intact blood-brain barrier. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[28]  Sumit Arora,et al.  Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers , 2012, International journal of nanomedicine.

[29]  M. Martins,et al.  Synthesis of an O-alkynyl-chitosan and its chemoselective conjugation with a PEG-like amino-azide through click chemistry. , 2012, Carbohydrate polymers.

[30]  B. Hyman,et al.  Nanoparticles enhance brain delivery of blood–brain barrier-impermeable probes for in vivo optical and magnetic resonance imaging , 2011, Proceedings of the National Academy of Sciences.

[31]  Yuping Bao,et al.  Water-soluble iron oxide nanoparticles with high stability and selective surface functionality. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[32]  Heng Huang,et al.  Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. , 2010, Nature nanotechnology.

[33]  C. Bianchi,et al.  One-step synthesis and functionalization of hydroxyl-decorated magnetite nanoparticles. , 2008, Journal of colloid and interface science.

[34]  Stefan Vogt,et al.  Synthesis, characterization, and in vitro testing of superparamagnetic iron oxide nanoparticles targeted using folic Acid-conjugated dendrimers. , 2008, ACS nano.

[35]  Klaus Funke,et al.  High- and low-frequency repetitive transcranial magnetic stimulation differentially activates c-Fos and zif268 protein expression in the rat brain , 2008, Experimental Brain Research.

[36]  William W. McDonald,et al.  Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial , 2007, Biological Psychiatry.

[37]  Á. Pascual-Leone,et al.  Noninvasive human brain stimulation. , 2007, Annual review of biomedical engineering.

[38]  J. Mink,et al.  Deep brain stimulation. , 2006, Annual review of neuroscience.

[39]  G. Jaouen,et al.  Labelling and binding of poly-(L-lysine) to functionalised gold surfaces. Combined FT-IRRAS and XPS characterisation. , 2001, Colloids and surfaces. B, Biointerfaces.

[40]  C M Epstein,et al.  Repetitive transcranial magnetic stimulation activates specific regions in rat brain. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A. Barker,et al.  NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX , 1985, The Lancet.

[42]  Y. Agrawal,et al.  Chitosan as a suitable nanocarrier material for anti-Alzheimer drug delivery. , 2015, International journal of biological macromolecules.

[43]  R Weissleder,et al.  Superparamagnetic iron oxide: pharmacokinetics and toxicity. , 1989, AJR. American journal of roentgenology.