Chapter 3
Ultrasound-Induced Treatment of Neurodegenerative Diseases across the Blood-Brain Barrier


Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly non-invasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood-brain barrier (BBB). The impermeability of the BBB is due to the tight junctions connecting adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and volume regulation to ensure conditions necessary for proper synaptic and axonal signaling. However, the same permeability properties that keep the brain healthy constitute the root of the difficulty in its pharmacological treatment. The BBB prevents most neurologically active drugs from entering the brain and, as a result, has been isolated as the rate-limiting factor in brain drag delivery. Until a solution to the trans-BBB delivery problem is found, treatments of neurological diseases will remain impeded. In this chapter, the role of focused ultrasound in the non-invasive and localized treatment of neurodegenerative disease is explored.

  • Abstract
  • 3.1 The Blood-Brain Barrier (BBB) Physiology: Structure and Function
  • 3.2 The BBB and Neurotherapeutics
  • 3.3 Focused Ultrasound (FUS)
  • 3.4 BBB Opening Using FUS and Microbubbles
  • 3.5 Clinical Significance
  • 3.5.1 Neurodegenerative Disease
  • 3.5.2 Drug Delivery in Neurodegenerative Disease
  • 3.5.3 FUS in Facilitating Drug Delivery in Neurodegenerative Disease
  • 3.6 Theoretical Studies on Transcranial Propagation and Thermal Effects, and Their Validation With Experiments
  • 3.7 In Vivo Feasibility of Noninvasive BBB Opening
  • 3.8 Duration of BBB Opening
  • 3.9 In Vivo Feasibility in Alzheimer's-Model (Amyloid Precursor Protein — APP) Mice
  • 3.10 Fluorescence Imaging Study of the Molecular Size Limit Traversing the BBB Opening
  • 3.11 Conclusions
  • References

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