Preclinical Research on Focused Ultrasound-Mediated Blood–Brain Barrier Opening for Neurological Disorders: A Review
Abstract
:1. Introduction
2. Current Status of FUS-Mediated BBB Opening
2.1. Alzheimer’s Disease
2.2. Parkinson’s Disease
2.3. Brain Tumor
3. Secondary Biological Effects
3.1. Neurogenesis
3.2. Glymphatic System
3.3. Inflammatory Response
4. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Alvarez, J.I.; Katayama, T.; Prat, A. Glial influence on the blood brain barrier. Glia 2013, 61, 1939–1958. [Google Scholar] [CrossRef] [PubMed]
- Arvanitis, C.D.; Ferraro, G.B.; Jain, R.K. The blood–brain barrier and blood–tumour barrier in brain tumours and metastases. Nat. Rev. Cancer 2020, 20, 26–41. [Google Scholar] [CrossRef] [PubMed]
- Zlokovic, B.V. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008, 57, 178–201. [Google Scholar] [CrossRef] [PubMed]
- Montagne, A.; Zhao, Z.; Zlokovic, B.V. Alzheimer’s disease: A matter of blood–brain barrier dysfunction? J. Exp. Med. 2017, 214, 3151–3169. [Google Scholar] [CrossRef] [PubMed]
- Venkataramani, V.; Tanev, D.I.; Strahle, C.; Studier-Fischer, A.; Fankhauser, L.; Kessler, T.; Körber, C.; Kardorff, M.; Ratliff, M.; Xie, R. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature 2019, 573, 532–538. [Google Scholar] [CrossRef]
- Allen, B.D.; Limoli, C.L. Breaking barriers: Neurodegenerative repercussions of radiotherapy induced damage on the blood-brain and blood-tumor barrier. Free Radic. Biol. Med. 2022, 178, 189–201. [Google Scholar] [CrossRef]
- Wang, D.; Wang, C.; Wang, L.; Chen, Y. A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment. Drug Deliv. 2019, 26, 551–565. [Google Scholar] [CrossRef]
- Griffith, J.I.; Rathi, S.; Zhang, W.; Zhang, W.; Drewes, L.R.; Sarkaria, J.N.; Elmquist, W.F. Addressing bbb heterogeneity: A new paradigm for drug delivery to brain tumors. Pharmaceutics 2020, 12, 1205. [Google Scholar] [CrossRef]
- Cordon-Cardo, C.; O’brien, J.; Boccia, J.; Casals, D.; Bertino, J.; Melamed, M. Expression of the multidrug resistance gene product (p-glycoprotein) in human normal and tumor tissues. J. Histochem. Cytochem. 1990, 38, 1277–1287. [Google Scholar] [CrossRef]
- Schinkel, A.H. P-glycoprotein, a gatekeeper in the blood–brain barrier. Adv. Drug Deliv. Rev. 1999, 36, 179–194. [Google Scholar] [CrossRef]
- Chen, Y.; Liu, L. Modern methods for delivery of drugs across the blood–brain barrier. Adv. Drug Deliv. Rev. 2012, 64, 640–665. [Google Scholar] [CrossRef]
- Shawkat, H.; Westwood, M.-M.; Mortimer, A. Mannitol: A review of its clinical uses. Contin. Educ. Anaesth. Crit. Care Pain 2012, 12, 82–85. [Google Scholar] [CrossRef]
- Dong, X. Current strategies for brain drug delivery. Theranostics 2018, 8, 1481. [Google Scholar] [CrossRef]
- Hynynen, K.; McDannold, N.; Vykhodtseva, N.; Jolesz, F.A. Noninvasive mr imaging–guided focal opening of the blood-brain barrier in rabbits. Radiology 2001, 220, 640–646. [Google Scholar] [CrossRef]
- Hynynen, K.; McDannold, N.; Sheikov, N.A.; Jolesz, F.A.; Vykhodtseva, N. Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage 2005, 24, 12–20. [Google Scholar] [CrossRef]
- Kong, C. Combined Therapy of Focused Ultrasound and Aducanumab Induces Neurogenesis and Decreases of Beta-Amyloid Plaques in a Mouse Model of Alzheimer’s Disease; Graduate School, Yonsei University: Seoul, Republic of Korea, 2022. [Google Scholar]
- Vyas, N.; Manmi, K.; Wang, Q.; Jadhav, A.J.; Barigou, M.; Sammons, R.L.; Kuehne, S.A.; Walmsley, A.D. Which parameters affect biofilm removal with acoustic cavitation? A review. Ultrasound Med. Biol. 2019, 45, 1044–1055. [Google Scholar] [CrossRef]
- Park, J.; Zhang, Y.; Vykhodtseva, N.; Jolesz, F.A.; McDannold, N.J. The kinetics of blood brain barrier permeability and targeted doxorubicin delivery into brain induced by focused ultrasound. J. Control. Release 2012, 162, 134–142. [Google Scholar] [CrossRef]
- Geerts, H.; Grossberg, G.T. Pharmacology of acetylcholinesterase inhibitors and n-methyl-d-aspartate receptors for combination therapy in the treatment of Alzheimer’s disease. J. Clin. Pharmacol. 2006, 46, 8S–16S. [Google Scholar] [CrossRef]
- Asher, S.; Priefer, R. Alzheimer’s disease failed clinical trials. Life Sci. 2022, 306, 120861. [Google Scholar] [CrossRef]
- Sevigny, J.; Chiao, P.; Bussière, T.; Weinreb, P.H.; Williams, L.; Maier, M.; Dunstan, R.; Salloway, S.; Chen, T.; Ling, Y. The antibody aducanumab reduces aβ plaques in Alzheimer’s disease. Nature 2016, 537, 50–56. [Google Scholar] [CrossRef]
- Walsh, S.; Merrick, R.; Milne, R.; Brayne, C. Aducanumab for Alzheimer’s disease? BMJ 2021, 374, n1682. [Google Scholar] [CrossRef] [PubMed]
- Jordão, J.F.; Ayala-Grosso, C.A.; Markham, K.; Huang, Y.; Chopra, R.; McLaurin, J.; Hynynen, K.; Aubert, I. Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-β plaque load in the tgcrnd8 mouse model of Alzheimer’s disease. PLoS ONE 2010, 5, e10549. [Google Scholar] [CrossRef] [PubMed]
- Alecou, T.; Giannakou, M.; Damianou, C. Amyloid β plaque reduction with antibodies crossing the blood-brain barrier, which was opened in 3 sessions of focused ultrasound in a rabbit model. J. Ultrasound Med. 2017, 36, 2257–2270. [Google Scholar] [CrossRef] [PubMed]
- Xhima, K.; Markham-Coultes, K.; Nedev, H.; Heinen, S.; Saragovi, H.; Hynynen, K.; Aubert, I. Focused ultrasound delivery of a selective trka agonist rescues cholinergic function in a mouse model of Alzheimer’s disease. Sci. Adv. 2020, 6, eaax6646. [Google Scholar] [CrossRef]
- Hsu, P.-H.; Lin, Y.-T.; Chung, Y.-H.; Lin, K.-J.; Yang, L.-Y.; Yen, T.-C.; Liu, H.-L. Focused ultrasound-induced blood-brain barrier opening enhances gsk-3 inhibitor delivery for amyloid-beta plaque reduction. Sci. Rep. 2018, 8, 12882. [Google Scholar] [CrossRef]
- Xhima, K.; Markham-Coultes, K.; Hahn Kofoed, R.; Saragovi, H.U.; Hynynen, K.; Aubert, I. Ultrasound delivery of a trka agonist confers neuroprotection to Alzheimer-associated pathologies. Brain 2022, 145, 2806–2822. [Google Scholar] [CrossRef]
- Dubey, S.; Heinen, S.; Krantic, S.; McLaurin, J.; Branch, D.R.; Hynynen, K.; Aubert, I. Clinically approved ivig delivered to the hippocampus with focused ultrasound promotes neurogenesis in a model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 2020, 117, 32691–32700. [Google Scholar] [CrossRef]
- Mi, X.; Du, H.; Guo, X.; Wu, Y.; Shen, L.; Luo, Y.; Wang, D.; Su, Q.; Xiang, R.; Yue, S.; et al. Asparagine endopeptidase-targeted ultrasound-responsive nanobubbles alleviate tau cleavage and amyloid-β deposition in an Alzheimer’s disease model. Acta Biomater. 2022, 141, 388–397. [Google Scholar] [CrossRef]
- Zhu, Q.; Xu, X.; Chen, B.; Liao, Y.; Guan, X.; He, Y.; Cui, H.; Rong, Y.; Liu, Z.; Xu, Y. Ultrasound-targeted microbubbles destruction assists dual delivery of beta-amyloid antibody and neural stem cells to restore neural function in transgenic mice of Alzheimer’s disease. Med. Phys. 2022, 49, 1357–1367. [Google Scholar] [CrossRef]
- Jordão, J.F.; Thévenot, E.; Markham-Coultes, K.; Scarcelli, T.; Weng, Y.-Q.; Xhima, K.; O’Reilly, M.; Huang, Y.; McLaurin, J.; Hynynen, K. Amyloid-β plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound. Exp. Neurol. 2013, 248, 16–29. [Google Scholar] [CrossRef] [Green Version]
- Leinenga, G.; Götz, J. Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. Sci. Transl. Med. 2015, 7, 278ra233. [Google Scholar] [CrossRef]
- Leinenga, G.; Koh, W.K.; Götz, J. Scanning ultrasound in the absence of blood-brain barrier opening is not sufficient to clear β-amyloid plaques in the app23 mouse model of Alzheimer’s disease. Brain Res. Bull. 2019, 153, 8–14. [Google Scholar] [CrossRef]
- Poon, C.T.; Shah, K.; Lin, C.; Tse, R.; Kim, K.K.; Mooney, S.; Aubert, I.; Stefanovic, B.; Hynynen, K. Time course of focused ultrasound effects on β-amyloid plaque pathology in the tgcrnd8 mouse model of Alzheimer’s disease. Sci. Rep. 2018, 8, 14061. [Google Scholar] [CrossRef]
- Karakatsani, M.E.; Kugelman, T.; Ji, R.; Murillo, M.; Wang, S.; Niimi, Y.; Small, S.A.; Duff, K.E.; Konofagou, E.E. Unilateral focused ultrasound-induced blood-brain barrier opening reduces phosphorylated tau from the rtg4510 mouse model. Theranostics 2019, 9, 5396. [Google Scholar] [CrossRef]
- Pandit, R.; Leinenga, G.; Götz, J. Repeated ultrasound treatment of tau transgenic mice clears neuronal tau by autophagy and improves behavioral functions. Theranostics 2019, 9, 3754–3767. [Google Scholar] [CrossRef]
- Burgess, A.; Dubey, S.; Yeung, S.; Hough, O.; Eterman, N.; Aubert, I.; Hynynen, K. Alzheimer disease in a mouse model: Mr imaging–guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. Radiology 2014, 273, 736. [Google Scholar] [CrossRef]
- Leinenga, G.; Götz, J. Safety and efficacy of scanning ultrasound treatment of aged app23 mice. Front. Neurosci. 2018, 12, 55. [Google Scholar] [CrossRef]
- Shin, J.; Kong, C.; Cho, J.S.; Lee, J.; Koh, C.S.; Yoon, M.-S.; Na, Y.C.; Chang, W.S.; Chang, J.W. Focused ultrasound–mediated noninvasive blood-brain barrier modulation: Preclinical examination of efficacy and safety in various sonication parameters. Neurosurg. Focus 2018, 44, E15. [Google Scholar] [CrossRef]
- Shen, Y.; Hua, L.; Yeh, C.K.; Shen, L.; Ying, M.; Zhang, Z.; Liu, G.; Li, S.; Chen, S.; Chen, X.; et al. Ultrasound with microbubbles improves memory, ameliorates pathology and modulates hippocampal proteomic changes in a triple transgenic mouse model of Alzheimer’s disease. Theranostics 2020, 10, 11794–11819. [Google Scholar] [CrossRef]
- Bard, F.; Cannon, C.; Barbour, R.; Burke, R.-L.; Games, D.; Grajeda, H.; Guido, T.; Hu, K.; Huang, J.; Johnson-Wood, K. Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med. 2000, 6, 916–919. [Google Scholar] [CrossRef] [Green Version]
- Kong, C.; Yang, E.-J.; Shin, J.; Park, J.; Kim, S.-H.; Park, S.-W.; Chang, W.S.; Lee, C.-H.; Kim, H.; Kim, H.-S. Enhanced delivery of a low dose of aducanumab via fus in 5× fad mice, an ad model. Transl. Neurodegener. 2022, 11, 57. [Google Scholar] [CrossRef] [PubMed]
- Scarcelli, T.; Jordão, J.F.; O’reilly, M.A.; Ellens, N.; Hynynen, K.; Aubert, I. Stimulation of hippocampal neurogenesis by transcranial focused ultrasound and microbubbles in adult mice. Brain Stimul. 2014, 7, 304–307. [Google Scholar] [CrossRef] [PubMed]
- Shin, J.; Kong, C.; Lee, J.; Choi, B.Y.; Sim, J.; Koh, C.S.; Park, M.; Na, Y.C.; Suh, S.W.; Chang, W.S. Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model. Alzheimer Res. Ther. 2019, 11, 110. [Google Scholar] [CrossRef] [PubMed]
- Blackmore, D.G.; Turpin, F.; Palliyaguru, T.; Evans, H.T.; Chicoteau, A.; Lee, W.; Pelekanos, M.; Nguyen, N.; Song, J.; Sullivan, R.K. Low-intensity ultrasound restores long-term potentiation and memory in senescent mice through pleiotropic mechanisms including nmdar signaling. Mol. Psychiatry 2021, 26, 6975–6991. [Google Scholar] [CrossRef]
- Mooney, S.J.; Shah, K.; Yeung, S.; Burgess, A.; Aubert, I.; Hynynen, K. Focused ultrasound-induced neurogenesis requires an increase in blood-brain barrier permeability. PLoS ONE 2016, 11, e0159892. [Google Scholar] [CrossRef]
- Niu, X.; Yu, K.; He, B. Transcranial focused ultrasound induces sustained synaptic plasticity in rat hippocampus. Brain Stimul. 2022, 15, 352–359. [Google Scholar] [CrossRef]
- Deng, Z.; Wang, J.; Xiao, Y.; Li, F.; Niu, L.; Liu, X.; Meng, L.; Zheng, H. Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-β-induced neurotoxicity. Theranostics 2021, 11, 4351. [Google Scholar] [CrossRef]
- Wang, F.; Wei, X.-X.; Chang, L.-S.; Dong, L.; Wang, Y.-L.; Li, N.-N. Ultrasound combined with microbubbles loading bdnf retrovirus to open bloodbrain barrier for treatment of Alzheimer’s disease. Front. Pharmacol. 2021, 12, 615104. [Google Scholar] [CrossRef]
- Leinenga, G.; Koh, W.K.; Götz, J. A comparative study of the effects of aducanumab and scanning ultrasound on amyloid plaques and behavior in the app23 mouse model of Alzheimer disease. Alzheimer’s Res. Ther. 2021, 13, 76. [Google Scholar] [CrossRef]
- Poon, C.; Pellow, C.; Hynynen, K. Neutrophil recruitment and leukocyte response following focused ultrasound and microbubble mediated blood-brain barrier treatments. Theranostics 2021, 11, 1655. [Google Scholar] [CrossRef]
- Sun, T.; Shi, Q.; Zhang, Y.; Power, C.; Hoesch, C.; Antonelli, S.; Schroeder, M.K.; Caldarone, B.J.; Taudte, N.; Schenk, M. Focused ultrasound with anti-pglu3 aβ enhances efficacy in Alzheimer’s disease-like mice via recruitment of peripheral immune cells. J. Control. Release 2021, 336, 443–456. [Google Scholar] [CrossRef]
- Luo, K.; Wang, Y.; Chen, W.-S.; Feng, X.; Liao, Y.; Chen, S.; Liu, Y.; Liao, C.; Chen, M.; Ao, L. Treatment combining focused ultrasound with gastrodin alleviates memory deficit and neuropathology in an Alzheimer’s disease-like experimental mouse model. Neural Plast. 2022, 2022, 5241449. [Google Scholar] [CrossRef]
- Bathini, P.; Sun, T.; Schenk, M.; Schilling, S.; McDannold, N.J.; Lemere, C.A. Acute effects of focused ultrasound-induced blood-brain barrier opening on anti-pyroglu3 abeta antibody delivery and immune responses. Biomolecules 2022, 12, 951. [Google Scholar] [CrossRef]
- Bajracharya, R.; Cruz, E.; Götz, J.; Nisbet, R.M. Ultrasound-mediated delivery of novel tau-specific monoclonal antibody enhances brain uptake but not therapeutic efficacy. J. Control. Release 2022, 349, 634–648. [Google Scholar] [CrossRef]
- Rodrigues e Silva, A.M.; Geldsetzer, F.; Holdorff, B.; Kielhorn, F.W.; Balzer-Geldsetzer, M.; Oertel, W.H.; Hurtig, H.; Dodel, R. Who was the man who discovered the “lewy bodies”? Mov. Disord. 2010, 25, 1765–1773. [Google Scholar] [CrossRef]
- Appel-Cresswell, S.; Vilarino-Guell, C.; Encarnacion, M.; Sherman, H.; Yu, I.; Shah, B.; Weir, D.; Thompson, C.; Szu-Tu, C.; Trinh, J. Alpha-synuclein p. H50q, a novel pathogenic mutation for Parkinson’s disease. Mov. Disord. 2013, 28, 811–813. [Google Scholar] [CrossRef]
- Choi-Lundberg, D.L.; Lin, Q.; Chang, Y.-N.; Chiang, Y.L.; Hay, C.M.; Mohajeri, H.; Davidson, B.L.; Bohn, M.C. Dopaminergic neurons protected from degeneration by gdnf gene therapy. Science 1997, 275, 838–841. [Google Scholar] [CrossRef]
- Kearns, C.M.; Gash, D.M. Gdnf protects nigral dopamine neurons against 6-hydroxydopamine in vivo. Brain Res. 1995, 672, 104–111. [Google Scholar] [CrossRef]
- Burke, R.E. GDNF as a candidate striatal target-derived neurotrophic factor for the development of substantia nigra dopamine neurons. J. Neural. Transm. Suppl. 2006, 70, 41–45. [Google Scholar]
- Kordower, J.H.; Emborg, M.E.; Bloch, J.; Ma, S.Y.; Chu, Y.; Leventhal, L.; McBride, J.; Chen, E.-Y.; Palfi, S.; Roitberg, B.Z. Neurodegeneration prevented by lentiviral vector delivery of gdnf in primate models of Parkinson’s disease. Science 2000, 290, 767–773. [Google Scholar] [CrossRef]
- Gash, D.M.; Zhang, Z.; Ovadia, A.; Cass, W.A.; Yi, A.; Simmerman, L.; Russell, D.; Martin, D.; Lapchak, P.A.; Collins, F. Functional recovery in Parkinsonian monkeys treated with gdnf. Nature 1996, 380, 252–255. [Google Scholar] [CrossRef] [PubMed]
- Grondin, R.; Zhang, Z.; Yi, A.; Cass, W.A.; Maswood, N.; Andersen, A.H.; Elsberry, D.D.; Klein, M.C.; Gerhardt, G.A.; Gash, D.M. Chronic, controlled gdnf infusion promotes structural and functional recovery in advanced Parkinsonian monkeys. Brain 2002, 125, 2191–2201. [Google Scholar] [CrossRef] [PubMed]
- Lang, A.E.; Gill, S.; Patel, N.K.; Lozano, A.; Nutt, J.G.; Penn, R.; Brooks, D.J.; Hotton, G.; Moro, E.; Heywood, P. Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease. Ann. Neurol. 2006, 59, 459–466. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.Y.; Hsieh, H.Y.; Chen, C.M.; Wu, S.R.; Tsai, C.H.; Huang, C.Y.; Hua, M.Y.; Wei, K.C.; Yeh, C.K.; Liu, H.L. Non-invasive, neuron-specific gene therapy by focused ultrasound-induced blood-brain barrier opening in Parkinson’s disease mouse model. J. Control. Release 2016, 235, 72–81. [Google Scholar] [CrossRef]
- Fan, C.-H.; Ting, C.-Y.; Lin, C.Y.; Chan, H.-L.; Chang, Y.-C.; Chen, Y.-Y.; Liu, H.-L.; Yeh, C.-K. Noninvasive, targeted and non-viral ultrasound-mediated gdnf-plasmid delivery for treatment of Parkinson’s disease. Sci. Rep. 2016, 6, 19579. [Google Scholar] [CrossRef]
- Yue, P.; Miao, W.; Gao, L.; Zhao, X.; Teng, J. Ultrasound-triggered effects of the microbubbles coupled to gdnf plasmid-loaded pegylated liposomes in a rat model of Parkinson’s disease. Front. Neurosci. 2018, 12, 222. [Google Scholar] [CrossRef]
- Grondin, R.; Zhang, Z.; Ai, Y.; Ding, F.; Walton, A.; Surgener, S.; Gerhardt, G.; Gash, D. Intraputamenal infusion of exogenous neurturin protein restores motor and dopaminergic function in the globus pallidus of mptp-lesioned rhesus monkeys. Cell Transplant. 2008, 17, 373–381. [Google Scholar] [CrossRef]
- Samiotaki, G.; Acosta, C.; Wang, S.; Konofagou, E.E. Enhanced delivery and bioactivity of the neurturin neurotrophic factor through focused ultrasound—Mediated blood—Brain barrier opening in vivo. J. Cereb. Blood Flow Metab. 2015, 35, 611–622. [Google Scholar] [CrossRef]
- Karakatsani, M.E.; Wang, S.; Samiotaki, G.; Kugelman, T.; Olumolade, O.O.; Acosta, C.; Sun, T.; Han, Y.; Kamimura, H.A.; Jackson-Lewis, V. Amelioration of the nigrostriatal pathway facilitated by ultrasound-mediated neurotrophic delivery in early Parkinson’s disease. J. Control. Release 2019, 303, 289–301. [Google Scholar] [CrossRef]
- Noroozian, Z.; Xhima, K.; Huang, Y.; Kaspar, B.K.; Kügler, S.; Hynynen, K.; Aubert, I. Mri-guided focused ultrasound for targeted delivery of raav to the brain. In Adeno-Associated Virus Vectors: Design and Delivery; Springer: Berlin/Heidelberg, Germany, 2019; pp. 177–197. [Google Scholar]
- Ji, R.; Smith, M.; Niimi, Y.; Karakatsani, M.E.; Murillo, M.F.; Jackson-Lewis, V.; Przedborski, S.; Konofagou, E.E. Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson’s disease mouse model. Sci. Rep. 2019, 9, 19402. [Google Scholar] [CrossRef]
- Lin, C.-Y.; Lin, Y.-C.; Huang, C.-Y.; Wu, S.-R.; Chen, C.-M.; Liu, H.-L. Ultrasound-responsive neurotrophic factor-loaded microbubble-liposome complex: Preclinical investigation for Parkinson’s disease treatment. J. Control. Release 2020, 321, 519–528. [Google Scholar] [CrossRef]
- Yan, Y.; Chen, Y.; Liu, Z.; Cai, F.; Niu, W.; Song, L.; Liang, H.; Su, Z.; Yu, B.; Yan, F. Brain delivery of curcumin through low-intensity ultrasound-induced blood–brain barrier opening via lipid-plga nanobubbles. Int. J. Nanomed. 2021, 16, 7433. [Google Scholar] [CrossRef]
- Wang, Y.; Luo, K.; Li, J.; Liao, Y.; Liao, C.; Chen, W.-S.; Chen, M.; Ao, L. Focused ultrasound promotes the delivery of gastrodin and enhances the protective effect on dopaminergic neurons in a mouse model of Parkinson’s disease. Front. Cell. Neurosci. 2022, 16, 884788. [Google Scholar] [CrossRef]
- Trinh, D.; Nash, J.; Goertz, D.; Hynynen, K.; Bulner, S.; Iqbal, U.; Keenan, J. Microbubble drug conjugate and focused ultrasound blood brain barrier delivery of aav-2 sirt-3. Drug Deliv. 2022, 29, 1176–1183. [Google Scholar] [CrossRef]
- DeCordova, S.; Shastri, A.; Tsolaki, A.G.; Yasmin, H.; Klein, L.; Singh, S.K.; Kishore, U. Molecular heterogeneity and immunosuppressive microenvironment in glioblastoma. Front. Immunol. 2020, 11, 1402. [Google Scholar] [CrossRef]
- Bunevicius, A.; McDannold, N.J.; Golby, A.J. Focused ultrasound strategies for brain tumor therapy. Oper. Neurosurg. 2020, 19, 9–18. [Google Scholar] [CrossRef]
- Treat, L.H.; McDannold, N.; Vykhodtseva, N.; Zhang, Y.; Tam, K.; Hynynen, K. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using mri-guided focused ultrasound. Int. J. Cancer 2007, 121, 901–907. [Google Scholar] [CrossRef]
- Wei, K.-C.; Chu, P.-C.; Wang, H.-Y.J.; Huang, C.-Y.; Chen, P.-Y.; Tsai, H.-C.; Lu, Y.-J.; Lee, P.-Y.; Tseng, I.-C.; Feng, L.-Y. Focused ultrasound-induced blood–brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: A preclinical study. PLoS ONE 2013, 8, e58995. [Google Scholar] [CrossRef]
- Liu, H.-L.; Huang, C.-Y.; Chen, J.-Y.; Wang, H.-Y.J.; Chen, P.-Y.; Wei, K.-C. Pharmacodynamic and therapeutic investigation of focused ultrasound-induced blood-brain barrier opening for enhanced temozolomide delivery in glioma treatment. PLoS ONE 2014, 9, e114311. [Google Scholar] [CrossRef]
- Liu, H.-L.; Hua, M.-Y.; Chen, P.-Y.; Chu, P.-C.; Pan, C.-H.; Yang, H.-W.; Huang, C.-Y.; Wang, J.-J.; Yen, T.-C.; Wei, K.-C. Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. Radiology 2010, 255, 415–425. [Google Scholar] [CrossRef]
- Chen, P.-Y.; Hsieh, H.-Y.; Huang, C.-Y.; Lin, C.-Y.; Wei, K.-C.; Liu, H.-L. Focused ultrasound-induced blood–brain barrier opening to enhance interleukin-12 delivery for brain tumor immunotherapy: A preclinical feasibility study. J. Transl. Med. 2015, 13, 93. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, P.-Y.; Wei, K.-C.; Liu, H.-L. Neural immune modulation and immunotherapy assisted by focused ultrasound induced blood-brain barrier opening. Hum. Vaccines Immunother. 2015, 11, 2682–2687. [Google Scholar] [CrossRef] [PubMed]
- Yonemori, K.; Tsuta, K.; Ono, M.; Shimizu, C.; Hirakawa, A.; Hasegawa, T.; Hatanaka, Y.; Narita, Y.; Shibui, S.; Fujiwara, Y. Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not her2/neu-positive breast cancer. Cancer Interdiscip. Int. J. Am. Cancer Soc. 2010, 116, 302–308. [Google Scholar] [CrossRef] [PubMed]
- Park, E.J.; Zhang, Y.Z.; Vykhodtseva, N.; McDannold, N. Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model. J. Control. Release 2012, 163, 277–284. [Google Scholar] [CrossRef]
- Kobus, T.; Zervantonakis, I.K.; Zhang, Y.; McDannold, N.J. Growth inhibition in a brain metastasis model by antibody delivery using focused ultrasound-mediated blood-brain barrier disruption. J. Control. Release 2016, 238, 281–288. [Google Scholar] [CrossRef]
- Schoen, S.; Kilinc, M.S.; Lee, H.; Guo, Y.; Degertekin, F.L.; Woodworth, G.F.; Arvanitis, C. Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound. Adv. Drug Deliv. Rev. 2022, 180, 114043. [Google Scholar] [CrossRef]
- Aryal, M.; Fischer, K.; Gentile, C.; Gitto, S.; Zhang, Y.-Z.; McDannold, N. Effects on p-glycoprotein expression after blood-brain barrier disruption using focused ultrasound and microbubbles. PLoS ONE 2017, 12, e0166061. [Google Scholar] [CrossRef]
- Alkins, R.; Burgess, A.; Kerbel, R.; Wels, W.S.; Hynynen, K. Early treatment of her2-amplified brain tumors with targeted nk-92 cells and focused ultrasound improves survival. Neuro-Oncology 2016, 18, 974–981. [Google Scholar] [CrossRef]
- Zhao, G.; Huang, Q.; Wang, F.; Zhang, X.; Hu, J.; Tan, Y.; Huang, N.; Wang, Z.; Wang, Z.; Cheng, Y. Targeted shrna-loaded liposome complex combined with focused ultrasound for blood brain barrier disruption and suppressing glioma growth. Cancer Lett. 2018, 418, 147–158. [Google Scholar] [CrossRef]
- Sun, T.; Zhang, Y.; Power, C.; Alexander, P.M.; Sutton, J.T.; Aryal, M.; Vykhodtseva, N.; Miller, E.L.; McDannold, N.J. Closed-loop control of targeted ultrasound drug delivery across the blood–brain/tumor barriers in a rat glioma model. Proc. Natl. Acad. Sci. USA 2017, 114, E10281–E10290. [Google Scholar] [CrossRef]
- Curley, C.T.; Mead, B.P.; Negron, K.; Kim, N.; Garrison, W.J.; Miller, G.W.; Kingsmore, K.M.; Thim, E.A.; Song, J.; Munson, J.M. Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection. Sci. Adv. 2020, 6, eaay1344. [Google Scholar] [CrossRef]
- Zhang, D.Y.; Dmello, C.; Chen, L.; Arrieta, V.A.; Gonzalez-Buendia, E.; Kane, J.R.; Magnusson, L.P.; Baran, A.; James, C.D.; Horbinski, C. Ultrasound-mediated delivery of paclitaxel for glioma: A comparative study of distribution, toxicity, and efficacy of albumin-bound versus cremophor formulationsus-delivered abx extends survival in gbm pdx mouse model. Clin. Cancer Res. 2020, 26, 477–486. [Google Scholar] [CrossRef]
- Yang, Q.; Zhou, Y.; Chen, J.; Huang, N.; Wang, Z.; Cheng, Y. Gene therapy for drug-resistant glioblastoma via lipid-polymer hybrid nanoparticles combined with focused ultrasound. Int. J. Nanomed. 2021, 16, 185. [Google Scholar] [CrossRef]
- McDannold, N.; Zhang, Y.; Supko, J.G.; Power, C.; Sun, T.; Vykhodtseva, N.; Golby, A.J.; Reardon, D.A. Blood-brain barrier disruption and delivery of irinotecan in a rat model using a clinical transcranial mri-guided focused ultrasound system. Sci. Rep. 2020, 10, 8766. [Google Scholar] [CrossRef]
- Englander, Z.K.; Wei, H.-J.; Pouliopoulos, A.N.; Bendau, E.; Upadhyayula, P.; Jan, C.-I.; Spinazzi, E.F.; Yoh, N.; Tazhibi, M.; McQuillan, N.M. Focused ultrasound mediated blood–brain barrier opening is safe and feasible in a murine pontine glioma model. Sci. Rep. 2021, 11, 6521. [Google Scholar] [CrossRef]
- Sheybani, N.D.; Breza, V.R.; Paul, S.; McCauley, K.S.; Berr, S.S.; Miller, G.W.; Neumann, K.D.; Price, R.J. Immunopet-informed sequence for focused ultrasound-targeted mcd47 blockade controls glioma. J. Control. Release 2021, 331, 19–29. [Google Scholar] [CrossRef]
- Ye, D.; Yuan, J.; Yue, Y.; Rubin, J.B.; Chen, H. Focused ultrasound-enhanced delivery of intranasally administered anti-programmed cell death-ligand 1 antibody to an intracranial murine glioma model. Pharmaceutics 2021, 13, 190. [Google Scholar] [CrossRef]
- Chen, K.-T.; Chai, W.-Y.; Lin, Y.-J.; Lin, C.-J.; Chen, P.-Y.; Tsai, H.-C.; Huang, C.-Y.; Kuo, J.S.; Liu, H.-L.; Wei, K.-C. Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors. Sci. Adv. 2021, 7, eabd0772. [Google Scholar] [CrossRef]
- Moon, H.; Hwang, K.; Nam, K.M.; Kim, Y.-S.; Ko, M.J.; Kim, H.R.; Lee, H.J.; Kim, M.J.; Kim, T.H.; Kang, K.-S. Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound. Biomater. Adv. 2022, 141, 213102. [Google Scholar] [CrossRef]
- Sheybani, N.D.; Witter, A.R.; Garrison, W.J.; Miller, G.W.; Price, R.J.; Bullock, T.N. Profiling of the immune landscape in murine glioblastoma following blood brain/tumor barrier disruption with mr image-guided focused ultrasound. J. Neuro-Oncol. 2022, 156, 109–122. [Google Scholar] [CrossRef]
- Mooney, S.J.; Nobrega, J.N.; Levitt, A.J.; Hynynen, K. Antidepressant effects of focused ultrasound induced blood-brain-barrier opening. Behav Brain Res. 2018, 342, 57–61. [Google Scholar] [CrossRef] [PubMed]
- Tobin, M.K.; Musaraca, K.; Disouky, A.; Shetti, A.; Bheri, A.; Honer, W.G.; Kim, N.; Dawe, R.J.; Bennett, D.A.; Arfanakis, K. Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell 2019, 24, 974–982.e973. [Google Scholar] [CrossRef] [PubMed]
- Boldrini, M.; Fulmore, C.A.; Tartt, A.N.; Simeon, L.R.; Pavlova, I.; Poposka, V.; Rosoklija, G.B.; Stankov, A.; Arango, V.; Dwork, A.J. Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell 2018, 22, 589–599.e585. [Google Scholar] [CrossRef] [PubMed]
- Jessen, N.A.; Munk, A.S.; Lundgaard, I.; Nedergaard, M. The glymphatic system: A beginner’s guide. Neurochem. Res. 2015, 40, 2583–2599. [Google Scholar] [CrossRef]
- Nedergaard, M.; Goldman, S.A. Glymphatic failure as a final common pathway to dementia. Science 2020, 370, 50–56. [Google Scholar] [CrossRef]
- Harrison, I.F.; Ismail, O.; Machhada, A.; Colgan, N.; Ohene, Y.; Nahavandi, P.; Ahmed, Z.; Fisher, A.; Meftah, S.; Murray, T.K. Impaired glymphatic function and clearance of tau in an Alzheimer’s disease model. Brain 2020, 143, 2576–2593. [Google Scholar] [CrossRef]
- Chen, H.-L.; Chen, P.-C.; Lu, C.-H.; Tsai, N.-W.; Yu, C.-C.; Chou, K.-H.; Lai, Y.-R.; Taoka, T.; Lin, W.-C. Associations among cognitive functions, plasma DNA, and diffusion tensor image along the perivascular space (dti-alps) in patients with Parkinson’s disease. Oxidative Med. Cell. Longev. 2021, 2021, 4034509. [Google Scholar] [CrossRef]
- Goulay, R.; Flament, J.; Gauberti, M.; Naveau, M.; Pasquet, N.; Gakuba, C.; Emery, E.; Hantraye, P.; Vivien, D.; Aron-Badin, R. Subarachnoid hemorrhage severely impairs brain parenchymal cerebrospinal fluid circulation in nonhuman primate. Stroke 2017, 48, 2301–2305. [Google Scholar] [CrossRef]
- Iliff, J.J.; Chen, M.J.; Plog, B.A.; Zeppenfeld, D.M.; Soltero, M.; Yang, L.; Singh, I.; Deane, R.; Nedergaard, M. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J. Neurosci. 2014, 34, 16180–16193. [Google Scholar] [CrossRef]
- Plog, B.A.; Mestre, H.; Olveda, G.E.; Sweeney, A.M.; Kenney, H.M.; Cove, A.; Dholakia, K.Y.; Tithof, J.; Nevins, T.D.; Lundgaard, I. Transcranial optical imaging reveals a pathway for optimizing the delivery of immunotherapeutics to the brain. JCI Insight 2018, 3, e120922. [Google Scholar] [CrossRef]
- Ren, H.; Luo, C.; Feng, Y.; Yao, X.; Shi, Z.; Liang, F.; Kang, J.X.; Wan, J.B.; Pei, Z.; Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system. FASEB J. 2017, 31, 282–293. [Google Scholar] [CrossRef] [Green Version]
- Liu, D.-x.; He, X.; Wu, D.; Zhang, Q.; Yang, C.; Liang, F.-y.; He, X.-f.; Dai, G.-y.; Pei, Z.; Lan, Y. Continuous theta burst stimulation facilitates the clearance efficiency of the glymphatic pathway in a mouse model of sleep deprivation. Neurosci. Lett. 2017, 653, 189–194. [Google Scholar] [CrossRef]
- von Holstein-Rathlou, S.; Petersen, N.C.; Nedergaard, M. Voluntary running enhances glymphatic influx in awake behaving, young mice. Neurosci. Lett. 2018, 662, 253–258. [Google Scholar] [CrossRef]
- Lee, Y.; Choi, Y.; Park, E.-J.; Kwon, S.; Kim, H.; Lee, J.Y.; Lee, D.S. Improvement of glymphatic–lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer’s disease model. Sci. Rep. 2020, 10, 16144. [Google Scholar] [CrossRef]
- Meng, Y.; Abrahao, A.; Heyn, C.C.; Bethune, A.J.; Huang, Y.; Pople, C.B.; Aubert, I.; Hamani, C.; Zinman, L.; Hynynen, K. Glymphatics visualization after focused ultrasound-induced blood–brain barrier opening in humans. Ann. Neurol. 2019, 86, 975–980. [Google Scholar] [CrossRef]
- Ye, D.; Chen, S.; Liu, Y.; Weixel, C.; Hu, Z.; Chen, H. Mechanically manipulate glymphatic transportation by ultrasound combined with microbubbles. bioRxiv 2022. [Google Scholar] [CrossRef]
- Iliff, J.J.; Wang, M.; Liao, Y.; Plogg, B.A.; Peng, W.; Gundersen, G.A.; Benveniste, H.; Vates, G.E.; Deane, R.; Goldman, S.A. A paravascular pathway facilitates csf flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci. Transl. Med. 2012, 4, ra111–ra147. [Google Scholar] [CrossRef]
- Kovacs, Z.I.; Burks, S.R.; Frank, J.A. Focused ultrasound with microbubbles induces sterile inflammatory response proportional to the blood brain barrier opening: Attention to experimental conditions. Theranostics 2018, 8, 2245. [Google Scholar] [CrossRef]
- Sinharay, S.; Tu, T.-W.; Kovacs, Z.I.; Schreiber-Stainthorp, W.; Sundby, M.; Zhang, X.; Papadakis, G.Z.; Reid, W.C.; Frank, J.A.; Hammoud, D.A. In vivo imaging of sterile microglial activation in rat brain after disrupting the blood-brain barrier with pulsed focused ultrasound:[18f] dpa-714 pet study. J. Neuroinflammation 2019, 16, 155. [Google Scholar] [CrossRef]
- McMahon, D.; Hynynen, K. Acute inflammatory response following increased blood-brain barrier permeability induced by focused ultrasound is dependent on microbubble dose. Theranostics 2017, 7, 3989. [Google Scholar] [CrossRef]
- Kovacs, Z.I.; Kim, S.; Jikaria, N.; Qureshi, F.; Milo, B.; Lewis, B.K.; Bresler, M.; Burks, S.R.; Frank, J.A. Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation. Proc. Natl. Acad. Sci. USA 2017, 114, E75–E84. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mathew, A.S.; Gorick, C.M.; Price, R.J. Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically-and biochemically-driven responses to focused ultrasound blood-brain barrier disruption. Theranostics 2021, 11, 9847. [Google Scholar] [CrossRef] [PubMed]
- McMahon, D.; Bendayan, R.; Hynynen, K. Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome. Sci. Rep. 2017, 7, 45657. [Google Scholar] [CrossRef] [PubMed]
- Ji, R.; Karakatsani, M.E.; Burgess, M.; Smith, M.; Murillo, M.F.; Konofagou, E.E. Cavitation-modulated inflammatory response following focused ultrasound blood-brain barrier opening. J. Control. Release 2021, 337, 458–471. [Google Scholar] [CrossRef]
- Choi, H.J.; Han, M.; Seo, H.; Park, C.Y.; Lee, E.-H.; Park, J. The new insight into the inflammatory response following focused ultrasound-mediated blood–brain barrier disruption. Fluids Barriers CNS 2022, 19, 103. [Google Scholar] [CrossRef]
- D’Haese, P.F.; Ranjan, M.; Song, A.; Haut, M.W.; Carpenter, J.; Dieb, G.; Najib, U.; Wang, P.; Mehta, R.I.; Chazen, J.L.; et al. Β-amyloid plaque reduction in the hippocampus after focused ultrasound-induced blood-brain barrier opening in Alzheimer’s disease. Front. Hum. Neurosci. 2020, 14, 593672. [Google Scholar] [CrossRef]
- Park, S.H.; Baik, K.; Jeon, S.; Chang, W.S.; Ye, B.S.; Chang, J.W. Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: A proof-of-concept study. Transl. Neurodegener. 2021, 10, 44. [Google Scholar] [CrossRef]
- Meng, Y.; Pople, C.B.; Huang, Y.; Jones, R.M.; Ottoy, J.; Goubran, M.; Oliveira, L.M.; Davidson, B.; Lawrence, L.S.; Lau, A.Z. Putaminal recombinant glucocerebrosidase delivery with magnetic resonance–guided focused ultrasound in Parkinson’s disease: A phase i study. Mov. Disord. 2022, 37, 2134–2139. [Google Scholar] [CrossRef]
- Huang, Y.; Meng, Y.; Pople, C.B.; Bethune, A.; Jones, R.M.; Abrahao, A.; Hamani, C.; Kalia, S.K.; Kalia, L.V.; Lipsman, N. Cavitation feedback control of focused ultrasound blood-brain barrier opening for drug delivery in patients with Parkinson’s disease. Pharmaceutics 2022, 14, 2607. [Google Scholar] [CrossRef]
- Park, S.H.; Kim, M.J.; Jung, H.H.; Chang, W.S.; Choi, H.S.; Rachmilevitch, I.; Zadicario, E.; Chang, J.W. Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. J. Neurosurg. 2020, 134, 475–483. [Google Scholar] [CrossRef]
- Park, S.H.; Kim, M.J.; Jung, H.H.; Chang, W.S.; Choi, H.S.; Rachmilevitch, I.; Zadicario, E.; Chang, J.W. One-year outcome of multiple blood–brain barrier disruptions with temozolomide for the treatment of glioblastoma. Front. Oncol. 2020, 10, 1663. [Google Scholar] [CrossRef]
Authors, Year of Publication | Animal Model | FUS Parameters | Target Region | Main Results |
---|---|---|---|---|
Xhima (2020) [25] | TgCRND8 mice | CF:1.68 MHz PRF:1 Hz TD:120 s AP: Maintained after decreasing to 25% based on subharmonic emissions | Basal forebrain | Delivery of D3 (peptidomimetic agonist of TrkA) to the basal forebrain via FUS activated the TrkA-related signaling cascades and increased cholinergic neurotransmission. |
Dubey (2020) [28] | TgCRND8 mice | CF:1.68 MHz PRF:1 Hz TD:120 s AP: 0.23 MPa (feedback controller) | Cortex and hippocampus | IVIg-FUS significantly increased neurogenesis. FUS alone and IVIg alone significantly reduced amyloid plaques. IVIg-FUS affects neurogenesis through the downregulation of TNF-α. |
Deng (2021) [48] | APP/PS1 transgenic mice | CF:1 MHz PRF:10 Hz TD:60 s AP:0.6 MPa | Posterior 3.5 Lateral 3.5 Ventral 3.5 (mm) | Proved the possibility of extracting exosomes from astrocytes through ultrasonic stimulation. Astrocyte-derived exosome was delivered to the brain after opening the BBB to confirm the amyloid clearance effect. |
Feng (2021) [49] | Sprague-Dawley rats Aβ (1–40) injection model | CF:1 MHz TD:60 s AP:0.8 MPa | Hippocampus | As a result of the delivery of MpLXSN-BDNF (modified MB with retrovirus-BDNF) through FUS, cognitive function is improved, and BDNF restores synaptic loss. |
Leinenga (2021) [50] | APP23 transgenic mice | CF:1 MHz PRF:10 Hz TD:6 s AP:0.7 MPa | Whole brain | The combined treatment of scanning ultrasound and Aducanumab induced the effect of reducing amyloid plaques in the hippocampus and restored cognitive function. |
Poon (2021) [51] | TgCRND8 mice | CF:1 MHz PRF:1 Hz TD:120 s AP:0.28–0.55 MPa | Hippocampi and cortices | FUS-mediated BBB opening treatment three to five times biweekly did not induce neutrophil recruitment or phagocytosis of amyloid plaques. |
Sun (2021) [52] | Aged APP/PS1dE9 mice | CF:278 kHz PRF:2 Hz TD:100 s AP:0.33 MPa | Hippocampi | FUS increased the delivery rate of 07/2a mAb (Fc-competent anti-pGlu3 Aβ monoclonal antibody) to the brain by 5.5 times. Co-treatment with FUS and 07/2a mAb induces greater effects on learning and memory recovery and increases synaptic puncta. |
Luo (2022) [53] | Kunming mice Aβ1–42 injection model | CF:1 MHz PRF:1 Hz TD:120 s Voltage: 200 mV | Hippocampus | FUS-Gastrodin treatment restored memory and alleviated neuropathology. FUS-Gastrodin reduced Aβ, tau, and P-tau and upregulated BDNF, synaptophysin, and PSD-95 in the hippocampus. |
Bathini (2022) [54] | APP/PS1dE9 transgenic mice | CF:278 kHz PRF:2 Hz TD:100 s AP:0.33 MPa | Cortex and hippocampus | 07/2a mAb (anti-pyroglutamate-3 Aβ antibody) delivered with FUS resulted in a 5- to 6-fold increase in the brain-to-blood antibody ratio after 4 and 72 h. FUS-07/2a mAb enhanced the immunoreactivity of resident Iba1+ and phagocytic CD68+ microglia. |
Bajracharya (2022) [55] | K3 mice (human 1N4R tau) | CF:1 MHz PRF:10 Hz TD:6 s AP:0.5 MPa | Whole brain | Repeated FUS-BBB opening reduces tau inclusions. FUS-BBB opening mediates delivery of RNF5 (tau-specific monoclonal antibody) increase brain uptake and accumulates in unclear cells within the pyramidal layer. |
Kong (2022) [42] | 5×FAD mice | CF:0.5 MHz PRF:1 Hz TD:120 s AP:0.25 MPa | Hippocampi | Combined therapy of FUS and Aducanumab decreases amyloid deposits, increases neurogenesis, and attenuates cognitive function deficits. |
Authors, Year of Publication | Animal Model | FUS Parameters | Target Region | Main Results |
---|---|---|---|---|
Ji (2019) [72] | C57BL/6 mice MPTP | CF:1.5 MHz PRF:10 Hz TD:60 s AP:0.45 MPa | Striatum and substantia nigra | FUS-Intranasal delivery increased TH immunoreactivity and improved motor control function. |
Lin (2020) [73] | Balb/c mice MPTP | CF:1 MHz PRF:10 Hz TD:180 s Voltage:85 V | Substantia nigra | BDNF or GDNF gene delivery through the UTMD system induces a neuroprotective effect. However, combined with the GDNF/BDNF gene delivery it did not produce benefits compared with individually delivering BDNF or GDNF genes. |
Yan (2021) [74] | C57BL6 mice MPTP | CF:1 MHz PRF:1 Hz TD:60 s AP:0.24–0.45 MPa | Cortex, striatum, and substantia nigra | Improves therapeutic efficacy by increasing the delivery rate of encapsulated curcumin through FUS. |
Yuhong (2022) [75] | C57BL/6J mice MPTP | CF:1 MHz PRF:1 Hz TD:60 s Voltage:100, 150, 200 mV | Striatum | FUS increased the delivery rate of gastrodin, which induces neuroprotective effects, by 1.8-fold. FUS-Gastrodin treatment increased the expression levels of Bcl-2, BDNF, PSD-95, and synaptophysin protein and decreased the levels of caspase-3 in the striatum. |
Trinh (2022) [76] | Sprague-Dawley rats | CF:1 MHz PRF:1 Hz TD:120 s AP:0.4 MPa | Striatum and substantia nigra | FUS-induced BBB permeability in the striatum and substantia nigra. SIRT3-myc (viral vector gene therapies for PD) was expressed only in the striatum. |
Authors, Year of Publication | Animal Model | FUS Parameters | Target Region | Main Results |
---|---|---|---|---|
McDannold (2020) [96] | Sprague-Dawley rats F98 glioma | CF:230 kHz PRF:1.1 Hz TD:55 s AP:119–186 kPa | Striatum (Tumor) | It was confirmed that the ExAblate Neuro low-frequency clinical TcMRgFUS system could stably open the BBB in a rat model. Although delivery of irinotecan to the brain was not neurotoxic, it was not effective in prolonging survival or reducing the growth of gliomas. |
Curley (2020) [93] | athymic nude mice U87 GBM | CF:1.1 MHz DC:0.5% TD:120 s AP:0.45–0.55 MPa | Striatum (Tumor) | Interstitial fluid transport in brain tumors is increased by FUS. FUS increased the dispersion of directly injected brain-penetrating nanoparticles through tumor tissue by >100%. |
Englander (2021) [97] | B6 mice PDGF-B + PTEN−/−p53−/− murine glioma | CF:1.5 MHz PRF:5 Hz TD:120 s AP:0.7 MPa | Pons (Tumor) | FUS increased the delivery rate of etoposide into the tumor site more than five times compared to the control group, but there was no difference in survival rate or inflammation. |
Sheybani (2021) [98] | C57BL/6 mice GL261 glioma | CF:1.1 MHz DC:0.5% TD:120 s AP:0.4 MPa | Striatum (Tumor) | [89Zr]-mCD47 (phagocytic immunotherapy) delivery with repeated FUS can significantly constrain tumor outgrowth and extend survival rate. |
Ye (2021) [99] | Swiss-Webster mice GL261 glioma | CF:1.5 MHz PRF:5 Hz TD:60 s AP:0.43 MPa | Brain stem (Tumor) | FUS-mediated intranasal delivery increased the delivery rate of anti-PD-L1 antibodies to the brain stem by 4.03-fold. |
Chen (2021) [100] | Fisher rats C6 glioma | CF:400 kHz PRF:1 Hz TD:120 s AP:0.81 MPa | Caudate putamen (Tumor) | CD4+ (helper TILs) and CD8+ (cytotoxic TILs) immunogenic responses were significantly increased after 7 days of FUS treatment. |
Moon (2022) [101] | BALB/c nude mice U87 GBM | CF:1 MHz PRF:1 Hz TD:60 s AP:1 W/cm2 | Cerebral hemisphere | Sonosensitive liposome-encapsulating doxorubicin enhances permeability by FUS-mediated BBB opening. The GBM cytotoxicity of IMP301-DC was significantly increased. |
Sheybani (2022) [102] | C57BL/6 mice GL261 glioma | CF:1.1 MHz PRF:1 Hz TD:120 s AP:0.4–0.6 MPa | Striatum (Tumor) | FUS-mediated BBB opening in gliomas transiently induces inflammatory effects. |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kong, C.; Chang, W.S. Preclinical Research on Focused Ultrasound-Mediated Blood–Brain Barrier Opening for Neurological Disorders: A Review. Neurol. Int. 2023, 15, 285-300. https://doi.org/10.3390/neurolint15010018
Kong C, Chang WS. Preclinical Research on Focused Ultrasound-Mediated Blood–Brain Barrier Opening for Neurological Disorders: A Review. Neurology International. 2023; 15(1):285-300. https://doi.org/10.3390/neurolint15010018
Chicago/Turabian StyleKong, Chanho, and Won Seok Chang. 2023. "Preclinical Research on Focused Ultrasound-Mediated Blood–Brain Barrier Opening for Neurological Disorders: A Review" Neurology International 15, no. 1: 285-300. https://doi.org/10.3390/neurolint15010018
APA StyleKong, C., & Chang, W. S. (2023). Preclinical Research on Focused Ultrasound-Mediated Blood–Brain Barrier Opening for Neurological Disorders: A Review. Neurology International, 15(1), 285-300. https://doi.org/10.3390/neurolint15010018