Transcranial Ultrasound Stimulation Improves Long-Term Functional Outcomes and Protects Against Brain Damage in Traumatic Brain Injury.

Author: Chen SF1,2, Su WS3, Wu CH4, Lan TH5,6, Yang FY7,8
Affiliation:
1Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan.
2Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan.
3Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Taipei, 11221, Taiwan.
4Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
5Departments of Psychiatry, National Yang-Ming University, Taipei, Taiwan.
6Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan.
7Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Taipei, 11221, Taiwan. fyyang@ym.edu.tw.
8Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan. fyyang@ym.edu.tw.
Conference/Journal: Mol Neurobiol.
Date published: 2018 Jan 30
Other: Special Notes: doi: 10.1007/s12035-018-0897-z. [Epub ahead of print] , Word Count: 234


The purpose of this study was to assess the long-term treatment efficacy of low-intensity pulsed ultrasound (LIPUS) on functional outcomes, brain edema, and the possible involvement of reactions in mice following traumatic brain injury (TBI). Mice subjected to controlled cortical impact injury received LIPUS treatment daily for a period of 4 weeks. The effects of LIPUS on edema were detected by MR imaging in the mouse brain at 148 days following TBI. Long-term functional outcomes of LIPUS stimulation were evaluated by behavioral analyses. One-way or two-way analysis of variance and Student's t test were used for statistical analyses, with a significant level of .05. Up to post-injury day 148, treatment with LIPUS significantly improved functional outcomes (all p < 0.05). LIPUS also significantly attenuated brain edema and neuronal death at day 148 after TBI (all p < 0.05). Furthermore, LIPUS reduced MMP9 activity, neutrophil infiltration, and microglial activation at day 1 or day 4 following TBI (all p < 0.05). Meanwhile, LIPUS increased the Bcl-2/Bax ratio and enhanced the phosphorylation of Bad and FOXO-1 at day 1 or day 4 following TBI (all p < 0.05). Almost 5 months of follow-up showed that the treatment efficacy of post-injury LIPUS stimulation on reduced brain edema and improved functional outcomes persisted over time after TBI. The neuroprotective effects of LIPUS are associated with a reduction of early inflammatory events and inhibition of apoptotic progression.

KEYWORDS: Apoptosis; Brain edema; Inflammation; Traumatic brain injury; Ultrasound

PMID: 29383687 DOI: 10.1007/s12035-018-0897-z

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