In Vivo Wireless Brain Stimulation Via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles

Overview

Journal Neurotherapeutics

Specialty Neurology

Date 2021 Jun 16

PMID 34131858

Citations 18

Authors

Tyler Nguyen

Jianhua Gao

Ping Wang

Abhignyan Nagesetti

Peter Andrews

Sehban Masood

Zoe Vriesman

Ping Liang

Sakhrat Khizroev

Xiaoming Jin

Affiliations

Soon will be listed here.

Abstract

Wireless and precise stimulation of deep brain structures could have important applications to study intact brain circuits and treat neurological disorders. Herein, we report that magnetoelectric nanoparticles (MENs) can be guided to a targeted brain region to stimulate brain activity with a magnetic field. We demonstrated the nanoparticles' capability to reliably evoke fast neuronal responses in cortical slices ex vivo. After fluorescently labeled MENs were intravenously injected and delivered to a targeted brain region by applying a magnetic field gradient, a magnetic field of low intensity (350-450 Oe) applied to the mouse head reliably evoked cortical activities, as revealed by two-photon and mesoscopic imaging of calcium signals and by an increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the magnetic stimulation caused significant increases in astrocytes and microglia. Thus, MENs could enable a non-invasive and contactless deep brain stimulation without the need of genetic manipulation.

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References

Chu C, Jablonska A, Lesniak W, Thomas A, Lan X, Linville R . Optimization of osmotic blood-brain barrier opening to enable intravital microscopy studies on drug delivery in mouse cortex. J Control Release. 2019; 317:312-321. DOI: 10.1016/j.jconrel.2019.11.019. View

Silasi G, Xiao D, Vanni M, Chen A, Murphy T . Intact skull chronic windows for mesoscopic wide-field imaging in awake mice. J Neurosci Methods. 2016; 267:141-9. PMC: 5075450. DOI: 10.1016/j.jneumeth.2016.04.012. View

Frohlich E . The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012; 7:5577-91. PMC: 3493258. DOI: 10.2147/IJN.S36111. View

Huang H, Delikanli S, Zeng H, Ferkey D, Pralle A . Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nat Nanotechnol. 2010; 5(8):602-6. DOI: 10.1038/nnano.2010.125. View

Kozielski K, Jahanshahi A, Gilbert H, Yu Y, Erin O, Francisco D . Nonresonant powering of injectable nanoelectrodes enables wireless deep brain stimulation in freely moving mice. Sci Adv. 2021; 7(3). PMC: 7806222. DOI: 10.1126/sciadv.abc4189. View

Bystritsky A, Korb A, Douglas P, Cohen M, Melega W, Mulgaonkar A . A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011; 4(3):125-36. DOI: 10.1016/j.brs.2011.03.007. View

Liedtke W, Edelmann W, Bieri P, Chiu F, Cowan N, Kucherlapati R . GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron. 1996; 17(4):607-15. DOI: 10.1016/s0896-6273(00)80194-4. View

Sollmann N, Hauck T, Tussis L, Ille S, Maurer S, Boeckh-Behrens T . Results on the spatial resolution of repetitive transcranial magnetic stimulation for cortical language mapping during object naming in healthy subjects. BMC Neurosci. 2016; 17(1):67. PMC: 5078936. DOI: 10.1186/s12868-016-0305-4. View

Koziara J, Lockman P, Allen D, Mumper R . The blood-brain barrier and brain drug delivery. J Nanosci Nanotechnol. 2006; 6(9-10):2712-35. DOI: 10.1166/jnn.2006.441. View

10.

Miniussi C, Cappa S, Cohen L, Floel A, Fregni F, Nitsche M . Efficacy of repetitive transcranial magnetic stimulation/transcranial direct current stimulation in cognitive neurorehabilitation. Brain Stimul. 2010; 1(4):326-36. DOI: 10.1016/j.brs.2008.07.002. View

11.

Bullitt E . Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol. 1990; 296(4):517-30. DOI: 10.1002/cne.902960402. View

12.

Kerlin A, Andermann M, Berezovskii V, Reid R . Broadly tuned response properties of diverse inhibitory neuron subtypes in mouse visual cortex. Neuron. 2010; 67(5):858-71. PMC: 3327881. DOI: 10.1016/j.neuron.2010.08.002. View

13.

Zhang Q, Fu B, Zhang Z . Borneol, a novel agent that improves central nervous system drug delivery by enhancing blood-brain barrier permeability. Drug Deliv. 2017; 24(1):1037-1044. PMC: 8241164. DOI: 10.1080/10717544.2017.1346002. View

14.

Hudson A . Genetic Reporters of Neuronal Activity: c-Fos and G-CaMP6. Methods Enzymol. 2018; 603:197-220. PMC: 6045948. DOI: 10.1016/bs.mie.2018.01.023. View

15.

Gradinaru V, Thompson K, Zhang F, Mogri M, Kay K, Schneider M . Targeting and readout strategies for fast optical neural control in vitro and in vivo. J Neurosci. 2007; 27(52):14231-8. PMC: 6673457. DOI: 10.1523/JNEUROSCI.3578-07.2007. View

16.

Okuda-Shimazaki J, Takaku S, Kanehira K, Sonezaki S, Taniguchi A . Effects of titanium dioxide nanoparticle aggregate size on gene expression. Int J Mol Sci. 2010; 11(6):2383-92. PMC: 2904923. DOI: 10.3390/ijms11062383. View

17.

Barson D, Hamodi A, Shen X, Lur G, Constable R, Cardin J . Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits. Nat Methods. 2019; 17(1):107-113. PMC: 6946863. DOI: 10.1038/s41592-019-0625-2. View

18.

Kaushik A, Jayant R, Nikkhah-Moshaie R, Bhardwaj V, Roy U, Huang Z . Magnetically guided central nervous system delivery and toxicity evaluation of magneto-electric nanocarriers. Sci Rep. 2016; 6:25309. PMC: 4855156. DOI: 10.1038/srep25309. View

19.

Yu Y, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y . Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci Transl Med. 2011; 3(84):84ra44. DOI: 10.1126/scitranslmed.3002230. View

20.

Wu B, Yu A . Quercetin inhibits c-fos, heat shock protein, and glial fibrillary acidic protein expression in injured astrocytes. J Neurosci Res. 2000; 62(5):730-6. DOI: 10.1002/1097-4547(20001201)62:5<730::AID-JNR13>3.0.CO;2-K. View