Neuroprotective Effect of Low-Intensity Transcranial Ultrasound Stimulation in Moderate Traumatic Brain Injury Rats.

Tao Zheng,Shuo Wu,Yi Yuan,Zhanqiu Wang,Xiaohan Wang,Defeng Liu,Juan Du,Yinglan Jin,Qinglei Shi,Lanxiang Liu

doi:10.3389/fnins.2020.00172

Abstract

Traumatic brain injury (TBI) is a kind of severe brain injury characterized with a high incidence rate and a high disability rate. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective method for improving the functional prognosis of TBI. The fractional anisotropy (FA) value and mean diffusivity (MD) value can be sensitive to abnormal brain structure and function and can thus be used to evaluate the effect of LITUS on TBI. Our purpose was to evaluate the therapeutic effect of LITUS in a moderate TBI rat model with FA and MD values. For our method, we used 45 male Sprague Dawley rats (15 sham normal, 15 TBI, and 15 LITUS treatment rats). We used single-shot spin echo echo-planar imaging sequences at 3.0T to obtain the DTI parameters. Parameters of FA and MD on the treated side of the injury cortex were measured to evaluate the therapeutic effect of LITUS in a TBI rat model. For FA and MD values, groups were compared by using a two-way analysis of variance for repeated measures, and this was followed by Tukey’s post hoc test. Differences were considered significant at P < 0.05. The results were that the FA value in the LITUS treatment group at 1 day after TBI was significantly higher than that in the control group (adjusted P = 0.0422) and significantly lower than that in the TBI group at 14, 21, and 35 days after TBI (adjusted P = 0.0015, 0.0064, and 0.0173, respectively). At the end of the scan time point, the differences between the two groups were not significant (adjusted P = 0.3242). The MD values in the LITUS treatment group were significantly higher in the early stage than that in the TBI group (adjusted P = 0.0167) and significantly lower at the following time points than in the TBI group. In conclusion, daily treatment with LITUS for 10 min effectively improved the brain damage in the Controlled Cortical Impact (CCI)-caused TBI model. FA and MD values can serve as evaluation indicators for the neuro-protective effect of LITUS.

Highlights

Traumatic brain injury (TBI) is a form of brain injury caused by trauma, and it has a high incidence and a high rate of disability
fractional anisotropy (FA) of Injury Cortex in TBI, low-intensity pulsed transcranial ultrasound (LITUS) Treatment, and Sham Control Groups For the Sham Control group, the FA value did not change at each time point, and the curve remained constant
FA and mean diffusivity (MD) of Contralateral Mirror Cortex in TBI, LITUS Treatment, and Sham Control Groups By measuring the FA and MD values of cortex of the same brain region on the contralateral mirror cortex, we found that there was no significant difference in FA and MD between TBI, LITUS, and Sham control groups

Summary

Introduction

Traumatic brain injury (TBI) is a form of brain injury caused by trauma, and it has a high incidence and a high rate of disability. Recent epidemiological studies have shown that more than 40 percent of people experience varying degrees of TBI, from mild to severe forms, during their lifetime (Zetterberg et al, 2013; Williams et al, 2018). Our previous study found that LITUS has a regulatory effect on the diffusion of brain water molecules, and this leads to a change in the apparent diffusion coefficient (ADC) value of brain tissue in the LITUS stimulation region (Yuan et al, 2017). Recent studies have shown that LITUS brain stimulation can awaken patients with severe post-TBI consciousness disorders, and patients can recover successfully under ultrasound stimulation (Monti et al, 2016). LITUS is a promising type of physical therapy for brain trauma

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