Ultrasonic cerebrospinal fluid clearance improves outcomes in hemorrhagic brain injury models.

Impaired clearance of the byproducts of aging and neurologic disease from the brain exacerbates disease progression and severity. We have developed a noninvasive, low intensity transcranial focused ultrasound protocol that facilitates the removal of pathogenic substances from the cerebrospinal fluid (CSF) and the brain interstitium. This protocol clears neurofilament light chain (NfL) - an aging byproduct - in aged mice and clears red blood cells (RBCs) from the central nervous system in two mouse models of hemorrhagic brain injury.

Wirelessly Powered-Electrically Conductive Polymer System for Stem Cell Enhanced Stroke Recovery.

Effective stroke recovery therapeutics remain limited. Stem cell therapies have yielded promising results, but the harsh ischemic environment of the post-stroke brain reduces their therapeutic potential. Previously, we developed a conductive polymer scaffold system that enabled stem cell delivery with simultaneous electrical modulation of the cells and surrounding neural environment.

Acoustomechanically activatable liposomes for ultrasonic drug uncaging.

Ultrasound-activatable drug-loaded nanocarriers enable noninvasive and spatiotemporally-precise on-demand drug delivery throughout the body. However, most systems for ultrasonic drug uncaging utilize cavitation or heating as the drug release mechanism and often incorporate relatively exotic excipients into the formulation that together limit the drug-loading potential, stability, and clinical translatability and applicability of these systems. Here we describe an alternate strategy for the design of such systems in which the acoustic impedance and osmolarity of the internal liquid phase of a drug-loaded particle is tuned to maximize ultrasound-induced drug release.

Noninvasive ultrasonic induction of cerebrospinal fluid flow enhances intrathecal drug delivery.

Intrathecal drug delivery is routinely used in the treatment and prophylaxis of varied central nervous system conditions, as doing so allows drugs to directly bypass the blood-brain barrier. However, the utility of this route of administration is limited by poor brain and spinal cord parenchymal drug uptake from the cerebrospinal fluid. We demonstrate that a simple noninvasive transcranial ultrasound protocol can significantly increase influx of cerebrospinal fluid into the perivascular spaces of the brain, to enhance the uptake of intrathecally administered drugs.