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Neuromodulation

Imagine if certain parts of the brain could be stimulated with just one machine without even requiring surgery. Ultrasound has the amazing properties of not damaging the tissue through which it propagates to reach its desired destination and being much more spatially-accurate than electromagnetic waves. The mechanism by which ultrasound modulates neuronal activity is based upon changes in the permeability of neuronal membranes leading, after a chain of intracellular molecular reactions, to a subsequent general de- or hyperpolarization of the membranes of neuronal populations and to a change in bioelectrical activity of the brain.

Recent experiments show that focal modulation of brain activity is possible and safe.


Tyler WJ, Tufail Y, Finsterwald M, et al. Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound. PLoS ONE. 2008; 3 (10): e3511.

Yoo SS, Bystritsky A, et al. Noninvasive brain stimulation using focused ultrasound. In: 14th European Congress of Clinical Neurophysiology and the 4th International Conference on Transcranial Magnetic and Direct Current Stimulation; 2011 Jun 21–25; Rome, Italy. Clin Neurophysiol; 2011. p. S52S53.

Velling VA, Shklyaruk SP. Modulation of the functional state of the brain with the aid of focused ultrasonic action. Neurosci Behav Physiol. 1988; 18 (5): 36975.


Sonoporation

Neuron a cell type that has been difficult to transfect. Focused ultrasound can cause size oscillations in injected or existing micro-bubbles at a targeted location within the body. This phenomenon is called stable cavitation. This causes a mechanical disruption in the cell wall and the cell is subsuquently succeptible to drug absorbtion. Additionally, stable cavitation creates an increased flow of fluid in a cell’s environment, which further enhances the uptake of drugs.

Recent research shows that sonoporation is a simple, effective and inexpensive means by which to preferentially transfect DNA into neuronal cells.


Fischer AJ, Stanke JJ, Omar G, et al. Ultrasound-mediated gene transfer into neuronal cells. J Biotechnol. 2006; 122 (4): 393411.

Liang HD, Tang J, Halliwell, M. Sonoporation, drug delivery, and gene therapy. Proc Inst of Mech Eng H. 2010; 224 (2): 34361.


Blood-brain barrier modulation

Impermeability of the blood-brain barrier (BBB) allows only 5% of the 7000 or so small-molecule drugs available to treat only a tiny fraction of these diseases. Unfortunately, safe and localized opening of the BBB has proven to be a significant challenge. Of the methods used for BBB disruption shown to be effective, focused ultrasound, in conjunction with microbubbles, is the only technique that can induce localized BBB opening noninvasively and regionally. The need for such medical application is great as millions of people suffer from neurodegenerative diseases and malignant brain neoplasms with little available medical treatment.

Studies show that BBB can be disrupted safely and transiently under specific acoustic pressures (under 0.45 MPa) and microbubble (diameter under 8 μm) conditions.


Konofagou EE, Tung YS, Choi J, et al. Ultrasound-induced blood-brain barrier opening. Curr Pharm Biotechnol. 2012; 13 (7): 133245.

Liu HL, Yang HW, Hua MY, et al. Enhanced therapeutic agent delivery through magnetic resonance imaging-monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status. Neurosurg Focus. 2012; 32 (1): E4.

Etame AB, Diaz RJ, Smith CA, et al. Focused ultrasound disruption of the blood-brain barrier: a new frontier for therapeutic delivery in molecular neurooncology. Neurosurg Focus. 2012; 32 (1): E3.


 

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