2352
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 62, NO. 10, OCTOBER 2015
Pulsed Transcranial Ultrasound Stimulation Immediately After The Ischemic Brain Injury is Neuroprotective Tengfei Guo, Hangdao Li, Yifan Lv, Hongyang Lu, Student Member, IEEE, Jinhai Niu, Junfeng Sun, Member, IEEE, Guo-Yuan Yang, Chuancheng Ren∗ , and Shanbao Tong∗ , Senior Member, IEEE
Abstract—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. Index Terms—Distal middle cerebral artery occlusion (dMCAO), rehabilitation, stroke, transcranial ultrasound stimulation, ultrasound therapy.
I. INTRODUCTION OTH rodent models and clinical trials have reported that facilitating the affected hemisphere or inhibiting the unaffected hemisphere could be neuroprotective in stroke [1]– [6]. The cortical facilitation or inhibition could be induced
B
Manuscript received October 9, 2014; revised February 25, 2015; accepted April 18, 2015. Date of publication April 28, 2015; date of current version September 16, 2015. This work was supported in part by the National Science Foundation of China under Grant 61371018. Asterisk indicates corresponding authors. T. Guo, H. Li, Y. Lv, H. Lu, J. Niu, J. Sun, and G.-Y. Yang are with the School of Biomedical Engineering, Shanghai Jiao Tong University. ∗ C. Ren is with the Neurology Department of the 5th People’s Hospital of Shanghai, Fudan Unversity, Shanghai, China (e-mail:
[email protected]). ∗ S. Tong is with the School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China (e-mail:
[email protected]). This paper has supplementary downloadable material available at http:// ieeexplore.ieee.org (File size: 4 MB). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TBME.2015.2427339
mechanically, electrically, or magnetically by sensory stimulation [4]–[6], transcranial magnetic stimulation (TMS) [1], or transcranial direct current stimulation (tDCS) [7], [8]. The stimulation could start immediately after the stroke, or at the rehabilitation stage [4]. The possible underlying mechanisms for such stimulation-based therapeutics might be relevant to the restoration of the balance of interhemispheric inhibition [7], [9]. Recent in vivo experiments have shown that low-frequency (
