Noninvasive Low-Intensity Focused Ultrasound Mediates Tissue Protection following Ischemic Stroke

Abstract

Objective and Impact Statement. This study examined the efficacy and safety of pulsed, low-intensity focused ultrasound (LIFU) and determined its ability to provide neuroprotection in a murine permanent middle cerebral artery occlusion (pMCAO) model. Introduction. Focused ultrasound (FUS) has emerged as a new therapeutic strategy for the treatment of ischemic stroke; however, its nonthrombolytic properties remain ill-defined. Therefore, we examined how LIFU influenced neuroprotection and vascular changes following stroke. Due to the critical role of leptomeningeal anastomoses or pial collateral vessels, in cerebral blood flow restoration and tissue protection following ischemic stroke, we also investigated their growth and remodeling. Methods. Mice were exposed to transcranial LIFU (fundamental frequency: 1.1 MHz, sonication duration: 300 ms, interstimulus interval: 3 s, pulse repetition frequency: 1 kHz, duty cycle per pulse: 50%, and peak negative pressure: -2.0 MPa) for 30 minutes following induction of pMCAO and then evaluated for infarct volume, blood-brain barrier (BBB) disruption, and pial collateral remodeling at 24 hrs post-pMCAO. Results. We found significant neuroprotection in mice exposed to LIFU compared to mock treatment. These findings correlated with a reduced area of IgG deposition in the cerebral cortex, suggesting attenuation of BBB breakdown under LIFU conditions. We also observed increased diameter of CD31-postive microvessels in the ischemic cortex. We observed no significant difference in pial collateral vessel size between FUS and mock treatment at 24 hrs post-pMCAO. Conclusion. Our data suggests that therapeutic use of LIFU may induce protection through microvascular remodeling that is not related to its thrombolytic activity.

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

“…4c), we observed that microglia in the LIPUS group exhibited longer process lengths and a higher number of processes. Mechanistically, LIPUS can facilitate this transition by potentially breaking down fibrin polymers 129 , thereby reducing the burden of clearance, or by enhancing glycolytic metabolism 127 through the activation of mechanosensitive channels 130 . Future experiments to apply LIPUS after scar tissue formation may help test these hypotheses and explore the potential to mitigate the scar formation during the chronic phase following microelectrode implantation.…”