Molecular Neurobiology

, Volume 55, Issue 8, pp 7079–7089 | Cite as

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

  • Szu-Fu Chen
  • Wei-Shen Su
  • Chun-Hu Wu
  • Tsuo-Hung Lan
  • Feng-Yi YangEmail author


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.


Ultrasound Traumatic brain injury Brain edema Apoptosis Inflammation 



This study was supported by grants from the Ministry of Science and Technology of Taiwan (no. MOST 105-2221-E-010-003, MOST 104-2314-B-010-003-MY3, and 101-2314-B-350-001-MY3), the Veterans General Hospitals University System of Taiwan Joint Research Program (VGHUST107-G7-6-1 and VGHUST106-G7-6-1), the Cheng Hsin General Hospital Foundation (no. CY10721, CY10622, and CHGH103-34), and the Biophotonics & Molecular Imaging Research Center.

Compliance with Ethical Standards

All procedures involving animals were conducted in accordance with the guidelines for the Care and Use of Laboratory Animals. This study protocol was approved by our Animal Care and Use Committee.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Physical Medicine and RehabilitationCheng Hsin General HospitalTaipeiTaiwan
  2. 2.Departments of Physiology and BiophysicsNational Defense Medical CenterTaipeiTaiwan
  3. 3.Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and EngineeringNational Yang-Ming UniversityTaipeiTaiwan
  4. 4.Graduate Institute of Life SciencesNational Defense Medical CenterTaipeiTaiwan
  5. 5.Departments of PsychiatryNational Yang-Ming UniversityTaipeiTaiwan
  6. 6.Department of PsychiatryTaichung Veterans General HospitalTaichungTaiwan
  7. 7.Biophotonics and Molecular Imaging Research CenterNational Yang-Ming UniversityTaipeiTaiwan

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