Pitt Shield

Novel Animal Model of Spontaneous Cerebral Petechial Hemorrhage Using Focused Ultrasound in Rats.

Authors: Yoon SY, Han M, Lee C, Lee EH, Kim M, Kim KT, Hwang JH, Na S, Park J, Park KS

<i>Background and Objectives:</i> Petechial cerebral hemorrhages can be caused by various factors, such as traumas, cerebral infarctions, and aging, and is related to the disruption of the blood-brain barrier or the cellular damage of blood vessels. However, there is no animal model that recapitulates cerebral petechial hemorrhages. <i>Materials and Methods:</i> Here, we implemented a petechial hemorrhage using a novel technology, i.e., microbubble-assisted focused ultrasound (MB + FUS). <i>Results:</i> This method increases the permeability of the blood-brain barrier by directly applying mechanical force to the vascular endothelial cells through cavitation of the microbubbles. Microbubble-enhanced cavitation has the advantage of controlling the degree and location of petechial hemorrhages. <i>Conclusions:</i> We thus generated a preclinical rat model using noninvasive focal MB + FUS. This method is histologically similar to actual petechial hemorrhages of the brain and allows the achievement of a physiologically resembling petechial hemorrhage. In the future, this method shall be considered as a useful animal model for studying the pathophysiology and treatment of petechial cerebral hemorrhages.

Introduction

Purpose Other
Study Objective To develop a noninvasive rat model of cerebral petechial hemorrhage using microbubble-assisted focused ultrasound (MB+FUS).
Animal model / Human subject Rat (Rattus norvegicus, Sprague-Dawley), age: 9-10 weeks, sex: male
Disease model Petechial cerebral hemorrhage
MRI or image guidance method MRI-guided
Targeted brain region(s) Caudate Putamen

Outcomes and Safety

Summary of Outcomes Microbubble-assisted focused ultrasound (MB + FUS) produced localized petechial cerebral hemorrhages in rats by increasing blood–brain barrier permeability via microbubble cavitation, with controllable degree and location and histological similarity to human petechial hemorrhages.
Duration of biological effect 48 h
Safety-related matter Microbubble-assisted FUS induced pressure-dependent petechial hemorrhage with associated edema and transient motor impairment. No cerebral infarction observed on TTC staining

Brain Region

Ultrasound Parameters

Ultrasound instrument MRgFUS (RK-100, FUS Instruments); single-element therapeutic FUS transducer
FUS Frequency 1.1 MHz
FUS Pressure 1.5, 1.8, 2.0 Mpa
Focal Characteristics focal depth: None; focal length: 60 mm; aperture size: 75 mm
Treatment frequency Single

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