Present situation and prospects about application of microelectrode array in study on acupuncture efficacy

Han Qing (韩清), Xu Ming-shu (徐鸣曙), Xu Jia (徐佳), Ge Lin-bao (葛林宝), Li Ming-zhe (李明哲), Zhang Ying-jie (张英杰)

1 Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China

2 Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China

3 Shanghai Qigong Research Institute, Shanghai 200030, China

4 Shanghai Research Center for Acupuncture & Meridian, Shanghai 201203, China

5 Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Present situation and prospects about application of microelectrode array in study on acupuncture efficacy

Han Qing (韩清)1, Xu Ming-shu (徐鸣曙)2, Xu Jia (徐佳)1, Ge Lin-bao (葛林宝)3,4, Li Ming-zhe (李明哲)2, Zhang Ying-jie (张英杰)5

1 Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China

2 Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China

3 Shanghai Qigong Research Institute, Shanghai 200030, China

4 Shanghai Research Center for Acupuncture & Meridian, Shanghai 201203, China

5 Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

As a component of traditional Chinese medical therapies, acupuncture therapy has been proven effective for many nervous system diseases[1-4], and has been proven in a large number of clinical and experimental studies[5-7]. Due to complexity of the human body, the functional mechanism of acupuncture therapy is related to many disciplines including neuroanatomy, neurophysiology, blood rheology, molecular biology, and cell biology[8]. As one of the mechanisms of acupuncture efficacy, studies related to electrophysiology are not common and are mostly limited in EEG and evoked potentials and long-term potentiation of synaptic plasticity[9], and the recording means are just glass microelectrodes or metal single electrode. Because of the complexity of the nerve electrical activities, even in the neighboring neurons, the electrophysiological features are often different. Therefore, for the purpose to reveal the electrophysiological mechanism of acupuncture therapy inregulating the nervous system, the recording technique with the single electrode is apparently insufficient in many ways. The recording technique with microelectrode array (MEA) is an invasive synchronous recording method to record and stimulate several sites synchronously, integrating several dozen or more micro acquisition unit components[10], for recording the action potentials and field potentials at the same time, greatly expanding the research means for electrophysiological study and suitable for the study on multiple cell activities of the nerve, retina and myocardial cells[11].

Currently, the main stream MEA refers to needle MEA (also termed Utah electrode) developed by University of Utah, and linear silicon electrode array (LSEA, also termed Michigan electrode) developed by University of Michigan, U.S.A. These two types of electrodes can be used for acute or chronic recording of the cell field potentials and a large number of single cell action potentials in the cerebral tissues.

In order to understand the present situation of the application of MEA technique for guiding the application of this technique in the field of acupuncture science, we reviewed the present situation about the application of MEA recording technique in the study of nerve cell electrical signals in vivo.

1 Applications in Medical Researches

1.1 Application for study of electrophysiology of the central nerve

1.1.1 Application in the inspection of brain signals

The recording technique of brain electrical signals has been applied abroad for many years. As early as in 1970s, overseas scholars recorded the electrophysiological change of the neurons with MEA technique[12]. In recent years, with the progress of microelectrode technique, the application of MEA recording technique in the basic study of neurology is progressing steadily. Some Japanese scholars recorded the long-term potentiation on the dendrite of CA1 pyramidal neurons with the microelectrode recording technique, in order to observe the protective effect of arachidonic acid diet for synaptic plasticity in aged rats[13]. Ding MC, et al[14]inserted MEA into the fourth level of the barrel cortex, approximately 700-900 μm below the cortex surface, and recorded the constant and stable nervous activities of the primary somatosensory cortex in anesthetized rats. Other scholars inserted the spherical Ag/AgCl microelectrode on the corresponding dura mater of cortex area dominating the right forepaw of the rats modeled with focal cerebral ischemia, and induced and recorded the field potential by stimulating the left ulnar nerve[15].

As for stability of the records, Liu XD, et al[16]implanted MEA into the cat cortex, recorded the nerve electrical signals regularly in the several months, and classified them by using clustering analysis algorithm and interspike interval. The results showed the changes took place day by day gradually within 1-2 months after the implantation of MEA, in the interface between the implanted electrode and brain tissue and then became quite stable. In order to enhance the accuracy and stability of long-term recording of MEA, Prasad A, et al[17]found out that when electrode impedance was in the scope of 40-150 kΩ, the nerve electrical signals were obtained most easily in the further study by implanting the tungsten MEA into somatosensory cortex of experimental animals.

Han M, et al[18]improved the MEA by coating the contact tips of MEA with iridium oxide, for processing the record in vivo and record in vitro respectively, different from 3 to 18 months, and for further processing the confirmatory test on the cochlear nucleus and central nucleus of the hypothalamus. The results showed that this type of MEA after implantation can record the action potentials of the nerve cells stably for as long as 566 d. It has been proven in the histopathology that after the long-term implantation, only very slight change took place in the neurons and spongiocyte.

Charvet G, et al[19]developed 3D MEA, i.e. BIOMEA (TM), the ability of which in recording the low amplitude spontaneous potentials and action potentials had been confirmed.

In recent years, the progress had been continuously obtained in the transmission of the signals by MEA technique. Borton DA, et al[20]developed wireless broadband neural signal recording system, which had been succeeded in the animal experiment of pig and primate.

The in vivo recording technique of the cerebral signal change started comparatively early in China, but there were few reports on the application of microelectrode or MEA technique. Liu N, et al[21]inserted the flexible MEA of four electrodes, each electrode of 250 μm in diameter, firmly on the dura mater of visual cortex area, without going through the dura mater, to compare the differences of the black and white checkerboard pattern and black and white flashing stimulation in the visual evoked potential (VEP). The results showed that MEA could effectively record VEP and the peak value of the evoked potential was remarkably higher in the black and white checkerboard pattern than in the black and white flashing stimulation, so as to believe that the record of evoked potential is feasible via the dura mater externally by MEA technique.

1.1.2 Application situation for recording the cerebral signals in acupuncture study

In recent years, some scholars at home and abroad applied the test of the brain signals by microelectrodesin acupuncture research. Xu ZH, et al[22-23]introduced the microelectrode technique into the research field on interference of cerebral ischemia by acupuncture, and recorded the influence of acupuncture to the changes of brain signals after brain ischemia by using unipolar electrode. The recording electrode, a unipolar glass electrode filled with 2 mol/L NaCl solution, 3-5 μm in tip and 1-3 MΩ in impedance, was inserted into hippocampal dentate gyrus granule cells, to record the potential of cellular field. Wang XY, et al[24]pushed the MEA into the nucleus tractus solitaries (NTS) and somatosensary cortex by using microelectrode propeller and successfully recorded the change of field potentials (FPs) and observed the obvious change of numerical value of epilepsy wave duration and seizure rate before and after electroacupuncture. This was the first report about the application of MEA technique in acupuncture research.

1.1.3 Application in testing the spinal cord electrical signals

Prasad A, et al[25]recorded the electrical signals at the face-cleaning behavior (including the repeated movements of the forelimb) of the rats and explored the relationship between the signals of conscious movement and elbow movement by implanting MEA into the spinal cord of the rats at C5-6level. The results showed that the extraction of movement signals from the cervical cord for reconstruction of the elbow movement was feasible. Arle JE, et al[26]further proved that MEA technique could be used in the study of the spinal cord and believed that this technique could not only help people to further understand the structure and functions of the spinal cord but also could be used as a therapeutic method for several spinal cord injuries.

Gad PN, et al[27]observed the change of the latency and amplitude of the spinal cord evoked potentials, by implanting the polyimide substrate MEA into the epidural area of the spinal cord in the non-injured adult rats.

In 2004, some scholars applied the MEA technique in the study about the treatment of cross-sectional spinal cord injury. Saigal R, et al[28]made a cross-sectional injury of T10, T11or T12in four adult male cats. After 2-4 weeks, the unipolar electrode linked with 30 pieces of fine threads was inserted into the scope 3 cm bilateral to the lumbar cord of the brain-removed cat, giving bipolar pulse stimulation of 40-50 Hz,200 μs, (32±19) μA. By the obsrvation of the dynamical, kinematical and myoelectric indexes, it was found out that this technique was precisely effective for the restoration of the functions after spinal cord injury.

Some American scholars developed two kinds of the neural prosthesis with MEA as the main structure, one kind containing nine independent metal iridium microelectrodes, and another kind containing silicon substrate MEA. These two kinds of neural prosthesis were respectively implanted into the sacral cord (the model was manifested by the evoked bladder dysfunction) of the cats modeled with chronic spinal cord injury, and then pulse stimulation was given in intensity of 100 μA, duration of 400 μs, and frequency of 20 Hz. It was found out that those two kinds of neural prosthesis could induce the elevation of the intravesical pressure larger than 40 mmHg or relaxation of the urethal sphincter, but the restorative effect for the bladder functions was not persistent[29].

Shen WX, et al implanted 10 microelectrodes into the spinal cord of the rabbits, by depth of 1.0-1.5 mm, and the electrical signals were collected and recorded by 128 channels of the neural signal processing system (Cerebus system). Several independent bipolar discharge waveforms in amplitude of (250±25) μV and wave length of (1.1±0.1) ms were successfully recorded in 9 channels. This result was further proved in the rat experiment[30]. Besides, they also inserted the microelectrode into T8section of SD rat, by depth of 680-800 μm, and the electrical signals in wave width of 0.6-1.3 ms and wave amplitude of 230-130 μV by Cerebus neural signal processing system[31].

1.1.4 Application in testing the electrical signals of the spine cord in acupuncture research.

In 1980s, some scholars already tested the electrical signals of the spinal cord by glass microelectrode by inserting the electrodes into the spinal cord along the medial aspect of the lateral sulcus of the spinal cord in T7-9sections, by depth of 738-2 500 μm, for observing the influence of acupuncture to the spinal dorsal horn cells to the harmful reaction of the internal organs. The electrodes were filled with sodium chloride solution or sodium acetate solution and the resistance of electrodes was at 10-15 MΩ[32].

He XL, et al[33]recorded the electrical activities of the spinal dorsal horn neurons, for using them in the study on the relationship between analgesia by strong and weak electroacupuncture and the negative feedback regulatory mechanism on pain of the nucleus raphe magnus, with the recording position in the spinal cord of T12-L1sections. In recent years, Zhou T, et al[34]recorded the discharge changes of the spinal neurons by using glass microelectrodes filled with 0.5 mol/L sodium acetate solution and at impedance of 5-15 MΩ, believing that manual acupuncture techniques at different frequencies could interfere with the transmitting, coding and processing procedure of the neural electrical information in the spinal dorsal horn level. Ma C, et al[35]successfully recorded the evoked potentials of the spinal dorsal horn C-fibers by inserting the tungsten wire microelectrode into the spinal cord 100-500 μm below the surface, discovering that electroacupuncture could inhibit the spinal dorsalneuron LTP caused by synaptic transmission anomalies due to the central sensitization of the spinal dorsal neurons . As for the application of MEA technique in the acupuncture research, there has been no relevant report on its application in recording the spinal electrical signals.

1.2 Application in testing the electrophysiological signals of the peripheral nerves

In the aspect to record the electrophysiological signals of the peripheral nerves, Wallman L, et al[36]reported in 1999 that by implanting the silicon substrate MEA into the sciatic nerve of the rats and stimulating the nerve root at the fifth lumbar cord, ten weeks after recovery, they recorded the signals of complex action potentials and found out that the stimulation to MEA could induce the muscular contraction of the lower limbs.

Branner A, et al[37]further proved the feasibility about the application of MEA in recording the electrical signals of the peripheral nerves. In the study on the sciatic nerve of the cat, they implanted the MEA into the sciatic nerve by high-speed insertion technique, and collected the complex action potentials in several recording electrodes under the stimulation of Kraft (or baked) electrodes. The complex action potentials recorded one hour after the insertion were just in slight change in comparison of the records before the insertion, and the stability period of the record and stimulation was as high as 60 h.

Aoyagia Y, et al[38]inserted the MEA into the dorsal root ganglion of the cat, and recorded 373 independent sensory signal units in 587 microelectrodes, and could maintain a large number of the records stably.

Heiduschka P, et al[39]implanted the polyimide substrate MEA into the interface between the optic nerve and autologous nerve. The results showed that the axons of the retinal ganglion cells could regenerate. After stimulating the retina, the electrical signals of the regenerated nerves were recorded via the implanted MEA, which further proves that the application of this technique has been mature in the study on the electrical signals of the peripheral nerves.

Currently, there is little report regarding the application of MEA technique in testing the electrical signals of the peripheral nerves.

2 Influence on Nerve Cells of MEA Implantation

Although MEA technique has been applied extensively at home and abroad in the research of the neuroscience, there is still dispute on whether its insertion into the tissues would cause injury to the cells. Branner A, et al[40]conducted two experiments successively, to study if the inserted MEA would cause injury to the peripheral nerves. In one experiment, wireless MEA was implanted into the sciatic nerves of the experimental animals, to test the movement function of the testing animals by walking on the animal treadmill. The results showed that the implantation of MEA did not induce any influence to the movement function. In another experiment, the MEA with linking wire was implanted into the sciatic nerves of the cats, to test the stimulating threshold value and record the sensory signals, two weeks and four weeks after the implantation. The results showed that surgery was greatly influential to the records of threshold stimulation and sensory activities, but the results from the histological observation of the experimental animals showed that the shape and fiber density of the inserted nerves were in normal status.

Feng ZY, et al[41]obtained similar conclusion in the experiment to record the potentials in hippocampus CA1 region of anesthesized rats. Namely, by moving the recording microelectrodes upward and downward by 200 μm, there was almost no influence on the records of forward and reverse evoked potentials. This result showed that the damage on linear MEA for nerve cell damage was very small and its testing performance was stable. The action potential discharge of CA1 nerve cells could be effectively recorded in the testing points of the MEA on the cell layer.

Kui RT, et al[42]believed that the injury of the nervous system after implantation of microelectrodes was an important issue and suggested that the current technology should be integrated with microfluidics technology by adding microfluidic cavity and pipeline, to realize the release of neurotrophin after implantation and promote the nutrition and regeneration of the injured nerves, so as to alleviate injury caused by implantation of microelectrodes.

Although dispute still exists about if the implantation of MEA would cause any injury to the nerve cells, no report has been seen about influence of the injury from MEA insertion to the records of cerebral electrical signals.

3 Summary

In summary, with development of microelectronics manufacturing technology in recent years, MEA technology develops rapidly, and the manufacturing materials also develop gradually from semiconductor silicon to high-compatibility biological materials. In view of the advantageous performance in integrating dozens and even hundreds of micro-acquisition unit components, small structure and fine damage to the nerve cells, the MEA can be applied to record the change of action potentials and field potentials of multiple cells at the same time, and maintain the stability of the records, beneficial to the study onreflecting characteristics of the group nerve cells, and providing an ideal platform for the study on electrophysiological functions of the cells. It has been proved by the previous studies that MEA could continuously and stably record the electrical signals in the hippocampus, cerebral cortex, cerebral nuclei, dura mater, spinal cord and dorsal horn neurons, dorsal root ganglion, nerve fiber, and optic nerve, providing a tool for the application of MEA recording technology in the study on mechanism of acupuncture effect.

It has been indicated by the studies on acupuncture analgesia for many years that the efficacy of acupuncture analgesia is a complicated procedure in which the local receptors of the acupoints produce the nervous impulse under the stimulation of acupuncture, to transmit from the periphery to the spine, brain stem, diencephalon, limbic system and basal ganglia, cerebral cortex, and then the centers of various class modulate pain signals and sensation and involve the humeral regulation. It has been proved by the relevant study on meridians, acupoints and Zang-fu organs that the regulatory effect of acupuncture on the internal organs is a reflex activity, and the neural signals are transmitted from acupoint area to the nerve fibers via the regulation of the spinal cord and brain region or nucleus, such as medulla ventrolateral area, solitary nucleus, hypothalamus paraventricular nucleus, etc., and then come out from the autonomic nerve to dominate the corresponding organs. Regardless of the effect of acupuncture analgesia or its regulatory effect on the internal organs, a large number of complex production and transmission of electrical signals exist in various links, and MEA can record the electrical signals of the cerebral nuclei, spinal cord and peripheral nerves relatively at multiple spots. It is significant to record those signals by MEA technique, and reveal the feature and regularity of the production and transmission of those electrical signals for discovering the mechanism of acupuncture effect.

As for the specificity of the acupoints, studies in recent years showed that the sensitization features exist in acupoints under pathological condition, manifested by the sensitization of pain, heat, electricity and light. As for the mechanism of the sensitization features of the acupoints, most scholars believe that after the pathological change of the internal organs, the nerve impulse takes place, and it’s partially transmitted to the center via the complex middle links and some other part of it is transmitted to the sensory nerve ending of the skin via the axon reflex. In fact, this type of nerve impulse is also the production, transmission and distribution of the electrical signals. The MEA technique can record the electrical signals of the central nerves and also can record the electrical signals transmitting in the peripheral nerves, which provides an important tool for the research about the sensitization and its mechanism of the acupoints.

Moreover, the promoting effect of acupuncture to neural plasticity has been concerned in recent years. Some achievements have been obtained in the studies on acupuncture in improving the structure of the synapse, density of the synapse, transmitting activities and long-term potentiation, and promoting the secretion of synaptophysin, synapse-associated proteins, nerve growth factor, and expressions of Bcl-2 gene and c-fos gene. Because the synaptic transmitting efficacy of the synaptic structure is mainly manifested by the transmission of the electrical signals, the MEA technique provides the support to the realization of the stable recording of the electrical signals of single cell and multiple cells, and to the electrophysiological study of acupuncture in promoting the plasticity of the nerves. If the breakthrough can be obtained in the application of this technique in the study of acupuncture in regulating the plasticity of the nerves, surely it will promote the great progress of acupuncture in preventing and treating some diseases of the nervous system.

Generally, the important mechanism in the efficacy of acupoints is supposed to induce the neural electrical signals, and regulate the neural electrical activities of the central nervous system, so as to display the regulatory effect for various functions of the organism. Because the neural electrical signals induced by acupuncture is the complex information of multiple channels and sites, the neural electrical information recorded by single microelectrode is apparently difficult to realize the recording of the neural signals of multiple sites. Therefore, the application of MEA technique in the study on the effect mechanism of acupuncture will be significant for observing and testing the complex electrical information of the nervous electrical activities induced by acupuncture, revealing the internal rules of the information in the production, transmission and coding process, and for explaining the electrophysiological mechanism of the acupuncture effect.

Conflict of Interest

The authors declared that there was no conflict of interest in this article.

Acknowledgments

This work was supported by National Natural Science Foundation of China (国家自然科学基金项目, No. 81001547); Shanghai Leading Academic Discipline Project (上海市重点学科项目, No. S30304); Cultivation Fund for Young Teacher in Shanghai Colleges and Universities (上海高校青年教师培养资助计划, No. ZZszy13052).

[1] Shi XM, Wang XW, Dai XY, Han JX, Li J, Bian JL, Li Y, Zhang HY, Zhao JG, Li JB, Gao SH. Clinical observation of acupuncture treatment for 4 728 cases of acute stage of cerebrovascular diseases. Proceedings of Sixth Tianjin International Conference on Acupuncture and Chinese Medicine Clinics, 2000: 3.

[2] Yang ZX, Bian JL, Xu JF, Shen PF, Xiong J, Guo JK, Zhang ZL, Li J, Shi XM. A multicenter randomized controlled trial of acupuncture for the convalescent stage of cerebral infarction-report on the assessment of therapeutic effects on syndrome in traditional Chinese medicine. Shanghai Zhenjiu Zazhi, 2008, 27(8): 3-6.

[3] He JQ, Zhao X. Recovery of acupuncture combined with rehabilitation treatment of 20 cases of muscle strength below traumatic spinal cord injury. Liaoning Zhongyi Zazhi, 2014, 41(2): 336-338.

[4] Jiang W, Jiang TK, Sun ZH, Lu Z. Clinical observation of Cang Gui Tan Xue needling method for sciatica. Shanghai Zhenjiu Zazhi, 2014, 33(7): 616-617.

[5] Ge LB, Fang C, Xu MS, Xu J, Li CZ, Cui XJ. Effects of electroacupuncture on the ability of learning and memory in rats with ischemia-reperfusion injury. J Acupunct Tuina Sci, 2009, 7(1): 3-7.

[6] Wang MS, Ma FG, Chen HL. Protective effects of acupuncture on brain tissue following ischemia/reperfusion injury. Neural Regen Res, 2008, 3(3): 309-312.

[7] Zhang C. A meta analysis on aacupuncture therapy treatment of trigeminal neuralgia curative effect. Zhonghua Zhongyiyao Xuekan, 2014, 32(2): 422-424.

[8] Xie XM, Wu P, Yang YK, Chen T, Zhang X. Progress of study on functional mechanism of acupuncture treatment for ischemic apoplexy. Zhongxiyi Jiehe Xinnaoxueguanbing Zazhi, 2011, 9(6): 738-740.

[9] Wang Y, Ma JQ, Han L, Shen Y, Wang S. Advances in electrophysiology of acupuncture intervening cerebral ischemia. Zhenjiu Linchuang Zazhi, 2012, 2(6): 81-84.

[10] Han Y. Development of microelectrode array system and its preliminary application in study on in vitro neural network. Master thesis of Academy of Military Medical Sciences, 2013.

[11] Na JN, Hou YM. History of action potentials recording technique and multiple microelectrode array recording technique and clinical application. Zhongguo Xinzang Qibo Yu Xindian Shengli Zazhi, 2005, 19(4): 307-309.

[12] Nicholson C, Llinas R. Real time current source-density analysis using multi-electrode array in cat cerebellum. Brain Res, 1975, 100(2): 418-424.

[13] Kotani S, Nakazawa H, Tokimasa T, Akimoto K, Kawashima H, Toyoda-Ono Y, Kiso Y, Okaichi H, Sakakibara M. Synaptic plasticity preserved with arachidonic acid diet in aged rats. Neurosci Res, 2003, 46(4): 453-461.

[14] Ding MC, Wang Q, Lo EH, Stanley GB. Cortical excitation and inhibition following focal traumatic brain injury. J Neurosci, 2011, 31(40): 14085-14094.

[15] Fujioka H, Kaneko H, Suzuki SS, Mabuchi K. Hyperexcitability-associated rapid plasticity after a focal cerebral ischemia. Stroke, 2004, 35(7): E346-E348.

[16] Liu XD, McCreery DB, Carter RR, Bullara LA, Yuen TG, Agnew WF. Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes. IEEE T Rehabil Eng, 1999, 7(3): 315-326.

[17] Prasad A, Sanchez JC. Quantifying long-term microelectrode array functionality using chronic in vivo impedance testing. J Neural Eng, 2012, 9(2): 026028.

[18] Han M, Manoonkitiwongsa PS, Wang CX, McCreery DB. In VIVO validation of custom-designed silicon-based microelectrode arrays for long-term neural recording and stimulation. IEEE T Bio-med Eng, 2012, 59(2): 346-354.

[19] Charvet G, Rousseau L, Billoint O, Gharbi S, Rostaing JP, Joucla S, Trevisiol M, Bourgerette A, Chauvet P, Moulin C. BioMEA (TM): A versatile high-density 3D microelectrode array system using integrated electronics. Biosens Bioelectron, 2010, 25(8): 1889-1896.

[20] Borton DA, Ming Yin, Aceros J, Nurmikko A. An implantable wireless neural interface for recording cortical circuit dynamics in moving primates. J Neural Eng, 2013, 10(2): 026010.

[21] Liu N, Shi WW, Chen LF, Hou WS, Yin ZQ. Recording visual cortex electrical activity through flexible microelectrode array implanted on duramater endocranium of cats. Disan Junyi Daxue Xuebao, 2011, 11: 1103-1105.

[22] Xu ZH, Xu NG, Yi W, Fu WB, Jing R. The improvement of synaptic plasticity in the rat dentate gyrus after stroke by acupuncture. Anhui Zhongyi Xueyuan Xuebao, 2007, 26(3): 18-23.

[23] Xu ZH, Xu NG, Yi W, Fu WB, Jing R. Effect of acupuncture at different doses on synaptic plasticity of rats after cerebral ischemia. Guangzhou Zhongyiyao Daxue Xuebao, 2009, 26(1): 32-37.

[24] Wang XY, Shang HY, He W, Shi H, Jing XH, Zhu B. Effects of transcutaneous electrostimulation auricular concha at different stimulating frequencies and duration on acute seizures in epilepsy rats. Zhen Ci Yan Jiu, 2012, 37(6): 447-452, 457.

[25] Prasad A, Sahin M. Extraction of motor activity from the cervical spinal cord of behaving rats. J Neural Eng, 2006, 3(4): 287-292.

[26] Arle JE, Shils JL, Malik WQ. Localized stimulation and recording in the spinal cord with microelectrode array//Annual International Conference of the IEEE Engineering in Medicine and Biology Society. San Diego, CA, 2012: 1851-1854.

[27] Gad PN, Choe J, Shah KG, Tooker A, Tolosa V, Pannu S, Garcia-Alias G, Zhong H, Gerasimenko Y, Roy RR, Edgerton VR. Using in vivo spinally-evoked potentials to assess functional connectivity along the spinal axis//Neural Engineering (NER), 2013 6th International IEEE/EMBS Conference on. San Diego, CA, 2013: 319-322.

[28] Saigal R, Renzi C, Mushahwar VK. Intraspinal microstimulation generates functional movements after spinal-cord injury. IEEE Trans Neural Syst Rehabil Eng, 2004, 12(4): 430-440.

[29] Mccreery D, Pikov V, Lossinsky A, Bullara L, Agnew W. Arrays for chronic functional microstimulation of the lumbosacral spinal cord. IEEE T Neur Sys Reh, 2004, 12(2): 195-207.

[30] Shen WX, Jiang ZL. A study on multi-electrode signals from spinal cord in rabbits. Nantong Daxue Xuebao: Yixue Ban, 2008, 28(3): 161-164.

[31] Shen WX, Yuan Y, Jiang ZL, Lu GM, Yao J. Experimental study of recording and analysing electrophysiological signals from corticospinal tract in rats. Zhongguo Yingyong Shenglixue Zazhi, 2011, 27(2): 168-172.

[32] Fang ZR, Hu K, Wang ZM, Li LN. Influence of acupuncture to visceral harmful reaction of spinal dorsal horn cell. Zhongguo Zhen Jiu, 1982, 2(4): 44-47.

[33] He XL, Liu X, Zhu B, Xu WD, Zhang SX. Extensive central mechanism of acupoints by strong electroacupuncture about analgesic effect of dorsal horn neurons. Acta Physiologica Sinica, 1995, 47(6): 605-609.

[34] Zhou T, Wang J, Han CX, Yisidatoulawo, Guo Y. Nonlinear dynamic analysis of electrical signals of wide dynamic range neurons in the spinal dorsal horn evoked by acupuncture manipulation at different frequencies. Zhongguo Zhongxiyi Jiehe Zazhi, 2012, 32(10): 1403-1406.

[35] Ma C, Feng KH, Yan LP. Effects of electroacupuncture on long-term potentiation of synaptic transmission in spinal dorsal horn in rats with neuropathic pain. Zhen Ci Yan Jiu, 2009, 34(5): 324-328.

[36] Wallman L, Levinsson A, Schouenborg J, Holmberg H, Montelius L, Danielsen N, Laurell T. Perforated Silicon nerve chips with doped registration electrodes: in vitro performance and in vivo operation. IEEE Trans Biomed Eng, 1999, 46(9): 1065-1073.

[37] Branner A, Normann RA. A multielectrode array for intrafascicular recording and stimulation in sciatic nerve of cats. Brain Res, 2000, 51(4): 293-306.

[38] Aoyagia Y, Richard BS, Brannerb A, Pearsona KG, Normannb RA. Capabilities of a penetrating microelectrode array for recording single units in dorsal root ganglia of the cat. J Neurosci Methods, 2003, 128(1/2): 9-20.

[39] Heiduschka P, Romann I, Stieglitz T, Thanos S. Perforated microelectrode arrays implanted in the regenerating adult central nervous system. Exp Neurol, 2001, 171(1): 1-10.

[40] Branner A, Stein RB, Fernandez E, Aoyagi Y, Normann RA. Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve. IEEE Trans Biomed Eng, 2004, 51(1): 146-157.

[41] Feng ZY, Guang L, Zheng XJ, Wang J, Li SH. Hippocampus field potentials and single cell action potentials tested by linear silicon electrode array. Shengwu Huaxue Yu Shengwu Wuli Jinzhan, 2007, 34(4): 401-407.

[42] Kui RT, Zhang F, Yu ZM. Research status of the microelectrode in the chronic neural electrophysiology experiment. Beijing Shengwu Yixue Gongcheng, 2008, 27(6): 651-654, 665.

Translator:Huang Guo-qi (黄国琪)

微电极阵列在针灸效应研究中的应用现状及前景

针灸疗法作为中医传统疗法的一部分，其对部分神经系统疾病的疗效已被大量的临床与实验研究所证实，然而现有常用的脑电图、诱发电位等电生理技术对于揭示针灸的作用机理尚有诸多不足之处。微电极阵列记录技术是起源于国外的生物电信号监测技术，属于电生理技术的一种，可在体或离体同时记录多个神经细胞的电信号，同时又保持记录信息的准确性、稳定性，较大程度丰富了电生理学研究的手段。该技术虽然在国外已经应用于基础研究和临床治疗，但是将该技术应用于针灸学领域的研究并不多见。对微电极阵列技术的在体应用情况进行综述，简要分析该技术应用于针灸学研究的现状及前景，以指导微电极阵列技术在针灸学研究领域的应用。

微电极; 电生理; 针灸疗法; 针刺疗法; 综述

R2-03 【

】A

Microelectrodes; Electrophysiology; Acupuncture-moxibustion Therapy; Acupuncture Therapy; Review

28 August 2014/Accepted: 20 October 2014

Author: Han Qing, 2012 master degree candidate

Xu Ming-shu, M.D., associate researcher.

E-mail: mingshuxu@163.com

As a component of traditional Chinese medical therapies, the therapeutic effects of acupuncture for some nervous system diseases have been proven by a large number of clinical and experimental studies. But, the electrophysiological techniques of the commonly used EEG and evoked potentials are still not sufficient to reveal the functional mechanism of acupuncture therapy. The recording technique of microelectrode array (MEA), a kind of electrophysiological technique originated from the overseas biological electrical signal monitoring technique, can be used to record multiple electrical signals of the nervous cells in vivo or in vitro, and maintain the accuracy and stability of the recorded information at the same time, which greatly enriches the means of electrophysiological study. This technique has been already applied in the basic study and clinical treatment abroad, but it is very seldom used in the study of acupuncture field. In order to guide the application of MEA in the research field of acupuncture science, a general survey about the application of MEA technique in vivo was done, and the present situation and prospects of the application of the technique in acupuncture science was briefly analyzed.