Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Neurosurg. 2010 Mar;112(3):539-48. doi: 10.3171/2009.7.JNS09787.
The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation-evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM).
The WINCS was used for FSCV, which consisted of a triangle wave scanned between -0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 microm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by approximately 50 microm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra.
The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV.
Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.
先前研究的作者已经证明，局部腺苷外排可能有助于丘脑深部脑刺激（DBS）治疗特发性震颤的作用机制。通过实时监测 DBS 靶向区域的神经化学输出，可能会通过识别参与 DBS 生理效应的候选神经递质和神经调质来推进功能性神经外科手术。这反过来又允许开发一种在体内化学引导 DBS 电极放置的方法。根据 FDA 认可的医疗电子设备安全标准设计，作者报告了无线即时神经递质浓度系统（WINCS）用于实时监测体内电刺激诱发的腺苷和多巴胺外排的效用，利用基于聚丙烯腈（T-650）碳纤维微电极（CFM）的快速扫描循环伏安法（FSCV）。
WINCS 用于 FSCV，它由在 400 V/秒的速率下在-0.4 至+1.5 V 之间扫描的三角波组成，并以 10 Hz 的频率施加。施加到 CFM 的所有电压均相对于 Ag/AgCl 参考电极。CFM 通过将单个 T-650 碳纤维（r=2.5 微米）吸入玻璃毛细管中并用移液管拉拔器拉成微尖端来构建。暴露的碳纤维（传感区）延伸超出玻璃绝缘约 50 微米。原理验证测试包括在体外测量腺苷和多巴胺，以及通过监测腹侧被盖区和黑质高频电刺激诱发的背侧尾状核壳中的腺苷和多巴胺外排，在麻醉的尿烷大鼠体内进行测量。
WINCS 提供了可靠的、高保真的腺苷外排测量。氧化峰电流出现在+1.5 V 和+1.0 V 处，用于腺苷，与多巴胺在+0.6 V 处的氧化峰电流分开。WINCS 在高频刺激腹侧被盖区和黑质时，在植入的 CFM 中检测到尾状核壳中的亚秒级腺苷和多巴胺外排。体外和体内测试均表明，WINCS 可以在存在其他易于氧化的神经化学物质（如多巴胺）的情况下检测到腺苷，与用于 FSCV 的常规硬连线电化学系统的检测能力相当。
总之，这些结果表明，WINCS 非常适合无线监测高频刺激诱发的脑细胞外腺苷浓度变化。选择性腺苷测量的临床应用可能对 DBS 技术的未来发展很重要。
