NEURONS BUT NOT GLIAL CELLS OVEREXPRESS UBIQUITIN IN THE RAT BRAIN FOLLOWING FOCUSED ULTRASOUND-INDUCED OPENING OF THE BLOOD-BRAIN BARRIER
NEURONS BUT NOT GLIAL CELLS OVEREXPRESS UBIQUITIN IN THE RAT BRAIN FOLLOWING FOCUSED ULTRASOUND-INDUCED OPENING OF THE BLOOD-BRAIN BARRIER
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DOI：
10.1016/j.neuroscience.2010.04.001
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发表时间：
2010-08-11
期刊：
影响因子：
3.3
通讯作者：
Meairs, S.
中科院分区：
文献类型：
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作者：
Alonso, A.;Reinz, E.;Meairs, S.
在超声造影剂存在的情况下，聚焦超声诱导血脑屏障(BBB)的开放是一种很有前途的靶向药物脑内传递的策略。我们研究的目的是确定超声治疗是否针对脑分子应激通路。利用较高水平的声压和微泡相结合，我们发现超声照射后6小时，神经元(每个光野11+/-3个泛素过表达细胞)中蛋白质泛素化水平增加，24小时后增加到16个(+/-4)标记细胞。Hsp70和Hsc70的表达在24小时内没有变化。超声处理后24小时(每个光野32+/-6个裂解半胱氨酸酶3阳性细胞)有限的凋亡。在凋亡的群体中只发现了神经元。尽管这些观察结果可能不适用于所有对BBB开放有用的声学参数，但它们表明，按照我们实验中使用的参数对大鼠大脑进行辐射是一种有用的工具，并诱导仅限于神经细胞的特定细胞应激反应。(C)2010年IBRO。爱思唯尔有限公司出版。保留所有权利。
Focused ultrasound-induced opening of the blood-brain barrier (BBB) in the presence of ultrasound contrast agents is a promising strategy for a targeted drug delivery to the brain. The aim of our study was to identify whether brain molecular stress pathways are targeted by ultrasound treatment. Using an upper level of acoustic pressures in combination with microbubbles, which have been previously reported as reliable for BBB opening without causing tissue damage, we found that ultrasound leads to an increased ubiquitinylation of proteins in neuronal (11 +/- 3 ubiquitin-overexpressing cells per optical field) but not glial cells 6 h post-insonation, increasing to 16 (+/- 4) labelled cells after 24 h. No changes in the expression of Hsp70 and Hsc70 were detected over 24 h. Ultrasound treatment was followed by limited apoptosis after 24 h (32 +/- 6 cleaved-caspase 3-positive cells per optical field) in the insonated areas. Only neurons were identified in the apoptotic population. Although these observations may not be applicable for all acoustic parameters useful for BBB opening, they demonstrate that insonation of the rat brain with the parameters used in our experiments is a useful tool for BBB opening and induces specific cellular stress response restricted to neuronal cells. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.