The new insight into the inflammatory response following focused ultrasound-mediated blood-brain barrier disruptionopen access
- Authors
- Choi, Hyo Jin; Han, Mun; Seo, Hyeon; Park, Chan Yuk; Lee, Eun-Hee; Park, Juyoung
- Issue Date
- Dec-2022
- Publisher
- BMC
- Keywords
- Blood-brain barrier; Focused ultrasound; Acute neuroinflammation; Genome profiling; Astrocyte
- Citation
- FLUIDS AND BARRIERS OF THE CNS, v.19, no.1
- Journal Title
- FLUIDS AND BARRIERS OF THE CNS
- Volume
- 19
- Number
- 1
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/86706
- DOI
- 10.1186/s12987-022-00402-3
- ISSN
- 2045-8118
- Abstract
- Background: Despite the great potential of FUS-BBB disruption (FUS-BBBD), it is still controversial whether FUS-BBBD acts as an inducing factor of neuro-inflammation or not, and the biological responses after FUS-BBBD triggers the inflammatory process are poorly understood. The aim of this study is to investigate the safety window for FUS levels based on a comprehensive safety assessment.Methods: The mice were treated with two different ultrasound parameters (0.25 MPa and 0.42 MPa) in the thalamus region of brain. The efficacy of BBB opening was verified by dynamic contrast-enhanced MRI (DCE-MRI) and the cavitation monitoring. The transcriptome analysis was performed to investigate the molecular response for the two BBBD conditions after FUS-mediated BBB opening in time-dependent manners. Histological analysis was used for evaluation of the tissue damage, neuronal degeneration, and activation of glial cells induced by FUS-BBBD.Results: The BBBD, as quantified by the Ktrans, was approximately threefold higher in 0.42 MPa-treated group than 0.25 MPa-treated group. While the minimal tissue/cellular damage was found in 0.25 MPa-treated group, visible damages containing microhemorrhages and degenerating neurons were detected in 0.42 MPa-treated group in accordance with the extent of BBBD. In transcriptome analysis, 0.42 MPa-treated group exhibited highly dynamic changes in the expression levels of an inflammatory response or NF-kappa B pathway-relative genes in a time-dependent manner whereas, 0.25 MPa was not altered. Interestingly, although it is clear that 0.42 MPa induces neuroinflammation through glial activation, neuroprotective properties were evident by the expression of A2-type astrocytes.Conclusions: Our findings propose that a well-defined BBBD parameter of 0.25 MPa could ensure the safety without cellular/tissue damage or sterile inflammatory response in the brain. Furthermore, the fact that the excessive sonication parameters at 0.42 MPa could induce a sterile inflammation response via glial activation suggested the possibility that could lead to tissue repair toward the homeostasis of the brain microenvironment through A2-type reactive astrocytes.
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