Abstract
The purpose of this study was to investigate the neuroprotective effects of low-intensity pulsed ultrasound (LIPUS) on behavioral and histological outcomes in a mouse model of traumatic brain injury (TBI). Mice subjected to controlled cortical impact injury were treated with LIPUS in the injured region daily for a period of 4 weeks. The effects of LIPUS on edema were observed by MR imaging in the mouse brain at 1 and 4 days following TBI. Brain water content, blood-brain barrier permeability, histology analysis, and behavioral studies were performed to assess the effects of LIPUS. Two-way analysis of variance and Student t test were used for statistical analyses, with a significant level of 0.05. Treatment with LIPUS significantly attenuated brain edema, blood-brain barrier permeability, and neuronal degeneration beginning at day 1. Compared with the TBI group, LIPUS also significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Post-injury LIPUS treatment reduced brain edema and improved behavioral and histological outcomes following TBI. The neuroprotective effects of LIPUS may be a promising new technique for treating TBI.
Highlights
Traumatic brain injury (TBI) is characterized by damage to the brain as a result of a mechanical force, a rapid acceleration-deceleration movement, or a blast wave
There were no Fluoro-Jade B (FJB)-positive degenerative neurons detected in the normal brain or the normal brain treated with 1-day or 4-day low-intensity pulsed ultrasound (LIPUS) (Fig. 2b)
We provide the first evidence that transcranial LIPUS stimulation improved long-term behavioral outcomes and attenuated brain edema in mice subjected to traumatic brain injury (TBI)
Summary
Traumatic brain injury (TBI) is characterized by damage to the brain as a result of a mechanical force, a rapid acceleration-deceleration movement, or a blast wave. The initial inflammatory response after TBI results in blood-brain barrier disruption (BBBD) and neuronal damage[2,3]. Focused ultrasound with microbubbles can locally disrupt the BBB for enhanced drug delivery, but this technology has almost always been found to be associated with sterile inflammatory response and damage can occur under inertial cavitation conditions[9,10,11]. One study suggests that the application of LIPUS in the early stages of TBI will effectively enhance the recovery of the BBB and alleviate the brain edema[18]. In the present study, we investigated the hypothesis that LIPUS stimulation may ameliorate brain edema, functional impairment, and neuronal damage after experimental TBI in mice. Our results have revealed novel neuroprotective effects of LIPUS on TBI, indicating the possibility that LIPUS may be useful in the treatment of brain injuries
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