Focal blood-brain-barrier disruption with high-frequency pulsed electric fields
Focal blood-brain-barrier disruption with high-frequency pulsed electric fields
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DOI：
10.1142/s2339547814500186
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发表时间：
2014-09-01
期刊：
影响因子：
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通讯作者：
Davalos, Rafael V.
中科院分区：
文献类型：
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作者：
Arena, Christopher B.;Garcia, Paulo A.;Davalos, Rafael V.
血脑屏障（BBB）是一种阻碍大分子转运的紧密连接网络，限制了全身化疗递送治疗恶性胶质瘤和其他神经系统疾病的有效性。在这里，我们提出了一种工具，用于BBB中断，使用亚微秒双极脉冲的突发，以增强大分子到大脑的转移。钝针电极被推进到麻醉的成年大鼠的运动皮层，并以250或2000 V/cm的电压-距离比、100 μ s的总编程通电时间和1 Hz的重复率传递一系列90 - 900次脉冲串。通过钆-伊文思蓝白蛋白示踪剂评估BBB破坏，发现所有实验条件在治疗后立即引起BBB破坏，而不诱导局部或远端肌肉收缩。最低能量条件下，300次爆发，由850 ns双极脉冲组成，导致显著的BBB破坏（0.51 cm（3）），而没有显示神经组织的坏死或凋亡损伤。
The blood-brain-barrier (BBB), a network of tight junctions that impedes large molecule transport, limits the usefulness of systemic chemotherapeutic delivery for the treatment of malignant gliomas and other neurological diseases. Here, we present a tool for BBB disruption that uses bursts of sub-microsecond bipolar pulses to enhance the transfer of large molecules to the brain. Blunt needle electrodes were advanced into the motor cortex of anesthetized adult rats, and a series of 90-900 bursts were delivered with voltage-to-distance ratios of 250 or 2000 V/cm, a total programmed energized time of 100 mu s, and a repetition rate of 1 Hz. BBB disruption was assessed via a gadolinium-Evans blue albumin tracer, and all experimental conditions were found to cause BBB disruption immediately following treatment without inducing local or distal muscle contractions. The lowest energy condition, 300 bursts consisting of 850 ns bipolar pulses, resulted in significant BBB disruption (0.51 cm(3)), without displaying necrotic or apoptotic damage to neurological tissue.