Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening.
Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening.
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DOI：
10.1038/srep15477
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发表时间：
2015-10-22
影响因子：
4.6
通讯作者：
Pei YC
中科院分区：
文献类型：
--
作者：
Chu PC;Liu HL;Lai HY;Lin CY;Tsai HC;Pei YC
脉冲聚焦超声（FUS）在血管系统中诱导微泡空化，并暂时破坏血脑屏障（BBB）以实现治疗药物的递送。然而，FUS诱导的血脑屏障开放是否伴有神经调节仍不清楚。在此，我们通过测量体感诱发电位（SSEPs）和血氧水平依赖（BOLD）反应的变化来表征FUS诱导的血脑屏障开放的功能效应。大鼠接受脉冲模式FUS（机械指数（MI）为0.3、0.55或0.8）作用于左侧初级体感皮层的前肢区域以诱导血脑屏障开放。进行长达1周的纵向测量以表征神经调节的时间动态。我们观察到，0.8 - MI的FUS显著抑制SSEP振幅并延长潜伏期，这种效应持续7天。0.55 - MI的FUS对SSEP产生最小且短期的抑制，持续时间不到60分钟，且不影响潜伏期。BOLD反应也以依赖于MI的方式受到抑制，这与对SSEPs的影响相似。此外，每3天重复给予0.55 - MI的FUS对SSEPs或组织完整性没有累积效应。这是第一个证明FUS诱导的血脑屏障开放伴有神经元反应可逆变化的证据，并可能为FUS诱导的血脑屏障开放在临床应用中的发展提供有价值的见解。
Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency, and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn’t affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses, and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications.