Affiliation:
1. Department of Neurosurgery, Brain Research Institute;
2. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul; and
3. Department of Neurosurgery, Catholic Kwandong University College of Medicine, International St. Mary’s Hospital, Incheon Metropolitan City, Korea
Abstract
OBJECTIVEThe application of pharmacological therapeutics in neurological disorders is limited by the ability of these agents to penetrate the blood-brain barrier (BBB). Focused ultrasound (FUS) has recently gained attention for its potential application as a method for locally opening the BBB and thereby facilitating drug delivery into the brain parenchyma. However, this method still requires optimization to maximize its safety and efficacy for clinical use. In the present study, the authors examined several sonication parameters of FUS influencing BBB opening in small animals.METHODSChanges in BBB permeability were observed during transcranial sonication using low-intensity FUS in 20 adult male Sprague-Dawley rats. The authors examined the effects of FUS sonication with different sonication parameters, varying acoustic pressure, center frequency, burst duration, microbubble (MB) type, MB dose, pulse repetition frequency (PRF), and total exposure time. The focal region of BBB opening was identified by Evans blue dye. Additionally, H & E staining was used to identify blood vessel damage.RESULTSAcoustic pressure amplitude and burst duration were closely associated with enhancement of BBB opening efficiency, but these parameters were also highly correlated with tissue damage in the sonicated region. In contrast, MB types, MB dose, total exposure time, and PRF had an influence on BBB opening without conspicuous tissue damage after FUS sonication.CONCLUSIONSThe study aimed to identify these influential conditions and provide safety and efficacy values for further studies. Future work based on the current results is anticipated to facilitate the implementation of FUS sonication for drug delivery in various CNS disease states in the near future.
Publisher
Journal of Neurosurgery Publishing Group (JNSPG)
Subject
Neurology (clinical),General Medicine,Surgery
Cited by
65 articles.
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