Pulsed Transcranial Ultrasound Stimulation Immediately After The Ischemic Brain Injury is Neuroprotective.

Abstract

We applied a low-intensity pulsed transcranial ultrasound stimulation (pTUS) to the ischemic cortex after a distal middle cerebral artery occlusion (dMCAO) to study whether pTUS is capable of protecting brain from ischemic injury. Rats were randomly assigned to Sham (n = 6), Control (n = 16), and pTUS (n = 16) groups. The pTUS-treated rats were subjected to 60-min ultrasonic stimulation immediately after the ischemia. After 48 h, the sensorimotor-related behavioral outcomes were assessed by a neurological severity score (NSS), and the permanent brain injury was assessed by the histologic analysis of TTC staining of brain slices. pTUS group showed significantly lower NSS (n = 10, 5.5 ± 2.5) than the Control group ( n = 10, 10.5 ±1.4) (p < 0.01). Concordantly, the ischemic lesion was significantly reduced after receiving pTUS immediately after dMCAO. The cortical infarct volume in the control group was more than threefold of the pTUS group (43.39% ± 2.33%, n = 16 versus 13.78% ± 8.18%, n = 16, p < 0.01). Immunohistochemical staining indicated reduction of neutrophils in the affected area, and laser speckle imaging showed significant increase of a cerebral blood flow after pTUS, which consistently supported the neuroprotection of pTUS in ischemic brain injury. Both behavior and histological results suggested that pTUS on ischemic core immediately after ischemic stroke could be neuroprotective. The noninvasiveness and high spatiotemporal resolution of pTUS makes it a unique neuromodulation technique in comparison with the current TMS and tDCS.