Multimodal evaluation of the effects of low-intensity ultrasound on cerebral blood flow after traumatic brain injury in mice.
Authors: Yi H, Wu S, Wang X, Liu L, Wang W, Yu Y, Li Z, Jin Y, Liu J, Zheng T, Du D
Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and destruction of the cerebrovascular system is a major factor in the cascade of secondary injuries caused by TBI. Laser speckle imaging (LSCI)has high sensitivity in detecting cerebral blood flow. LSCI can visually show that transcranial focused ultrasound stimulation (tFUS) treatment stimulates angiogenesis and increases blood flow. To study the effect of tFUS on promoting angiogenesis in Controlled Cortical impact (CCI) model. tFUS was administered daily for 10 min and for 14 consecutive days after TBI. Cerebral blood flow was measured by LSCI at 1, 3, 7 and 14 days after trauma. Functional outcomes were assessed using LSCI and neurological severity score (NSS). After the last test, Nissl staining and vascular endothelial growth factor (VEGF) were used to assess neuropathology. TBI can cause the destruction of cerebrovascular system. Blood flow was significantly increased in TBI treated with tFUS. LSCI, behavioral and histological findings suggest that tFUS treatment can promote angiogenesis after TBI.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
To evaluate whether daily transcranial focused ultrasound stimulation (tFUS) promotes angiogenesis, increases cerebral blood flow, and improves functional recovery after traumatic brain injury in a controlled cortical impact mouse model.
Animal model / Human subject
Mouse, C57BL/6, adult, male
Disease model
Traumatic brain injury (TBI)
Targeted brain region(s)
Injured Cortical Area, Parietal Lobe
Target coordinates
AP: 2mm behind bregma; ML: 2 mm left of midline; DV: none
Outcomes and Safety
Summary of Outcomes
tFUS improved blood flow, neurological recovery, neuronal survival, and transient VEGF-expression after TBI
Duration of biological effect
14 days
Safety-related matter
No adverse effects were reported in this study; the CCI parameters were chosen to avoid massive bleeding and reduce subdural hemorrhage. The authors also cite a pig study (Kenichiro et al.) reporting increased angiogenesis with tFUS “without any adverse reactions.”
Brain Region
Ultrasound Parameters
Ultrasound instrument
Unfocused ultrasound transducer V301-SU (Olympus) with conial collimator
FUS Frequency
500 kHz
FUS Intensity
2.6 W/cm2
FUS Mode
pulsed
Pulse duration
0.5 ms
Duration of a single FUS session
10 min
Focal Characteristics
focal depth: None; focal length: None; aperture size: None
Treatment frequency
multiple sessions
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