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

Goal: 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. Methods: 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. Results: 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. Conclusion: Both behavior and histological results suggested that pTUS on ischemic core immediately after ischemic stroke could be neuroprotective. Significance: The noninvasiveness and high spatiotemporal resolution of pTUS makes it a unique neuromodulation technique in comparison with the current TMS and tDCS.