The new insight into the inflammatory response following focused ultrasound-mediated blood-brain barrier disruption.
The new insight into the inflammatory response following focused ultrasound-mediated blood-brain barrier disruption.
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DOI：
10.1186/s12987-022-00402-3
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发表时间：
2022-12-23
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管FUS-BBBD（FUS-BBB disruption）具有很大的潜力，但FUS-BBBD是否作为神经炎症的诱导因子仍存在争议，并且FUS-BBBD触发炎症过程后的生物学反应也知之甚少。本研究的目的是在全面安全性评估的基础上研究FUS水平的安全窗口。用两种不同的超声参数（0.25 MPa和0.42 MPa）处理小鼠大脑丘脑区。通过动态增强MRI（DCE-MRI）和空洞监测来验证BBB开放的有效性。进行转录组分析以研究在FUS介导的BBB以时间依赖性方式开放后两种BBBD条件的分子响应。组织学分析用于评估由FUS-BBBD诱导的组织损伤、神经元变性和胶质细胞活化。通过Ktranss定量的BBBD在0.42 MPa处理组中比0.25 MPa处理组高约3倍。0.25 MPa组组织/细胞损伤最小，0.42 MPa组可见微血管增生和神经元变性，与BBBD的程度一致。在转录组分析中，0.42 MPa处理组以时间依赖性方式表现出炎症反应或NF-κB通路相关基因表达水平的高度动态变化，而0.25 MPa没有改变。有趣的是，虽然很明显，0.42 MPa诱导神经炎症通过神经胶质细胞活化，神经保护特性是明显的A2型星形胶质细胞的表达。我们的研究结果表明，0.25 MPa的明确BBBD参数可以确保安全性，而不会造成细胞/组织损伤或大脑中的无菌炎症反应。此外，0.42 MPa下的过度超声参数可通过胶质细胞活化诱导无菌炎症反应的事实表明，可能通过A2型反应性星形胶质细胞导致组织修复朝向脑微环境的稳态。在线版本包含补充材料，可通过10.1186/s12987-022-00402-3获得。
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. 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. 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-κB 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. 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. The online version contains supplementary material available at 10.1186/s12987-022-00402-3.
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影响因子：
19.7
作者：
Hynynen, K;McDannold, N;Jolesz, FA
通讯作者：
Jolesz, FA
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
5.7
作者：
Hynynen, K;McDannold, N;Vykhodtseva, N
通讯作者：
Vykhodtseva, N
DOI：
10.1073/pnas.0604318103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Kinoshita, Manabu;McDannold, Nathan;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo
影响因子：
1.2
作者：
Hayakawa, Kazuhide;Pham, Loc-Duyen D.;Arai, Ken;Lo, Eng H.
通讯作者：
Lo, Eng H.