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국회도서관 홈으로 정보검색 소장정보 검색
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결과 내 검색 동의어 포함

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Title Page

ABSTRACT

Contents

Chapter 1. Introduction 11

1.1. Research Background 11

Chapter 2. Parkinson's disease diagnosis and treatment 19

2.1. Material and Methods 19

2.1.1. Animals 19

2.1.2. 6 OHDA-induced parkinsonian rat 19

2.1.3. Gait test 20

2.1.4. Immunohistochemistry 20

2.1.5. Graphene electrode fabrication and stimulation 21

2.1.6. Treatment effect according to stimulation location (Electrotherapy) 21

2.1.7. Wireless device 22

2.1.8. Brainwave analysis 22

2.1.9. Brain slice preparation 23

2.1.10. Extracellular field recording 23

2.1.11. RNA sequencing 24

2.1.12. Differential expression analysis and data visualization 24

2.1.13. Statistics 24

2.2. Results 25

2.2.1. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats improves motor function 29

2.2.2. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats decreases high-frequency brain waves and increases low-frequency brain waves. 34

2.2.3. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats enhances mGluR-mediated, long-term synaptic plasticity. 37

2.2.4. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats alters gene expression in the glutamatergic synapse pathway. 41

2.3. Discussion 43

References 54

국문초록 59

List of Tables

Table 2.1. Specifications of NeuroStim (This work) and comparison with other wireless headstages. 46

Table 2.2. Statistical summary related to Fig 2.7D. Data are shown as means ± standard errors of the means. Independent sample t tests were used for the comparisons. 47

Table 2.3. Statistical summary related to Fig 2.7E-G. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way analysis of variance(ANOVA). 48

Table 2.4. Statistical summary related to Fig 2.9C. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way analysis of variance(ANOVA). 49

Table 2.5. Statistical summary related to Fig 2.11C. and Fig 2.11H. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way... 50

Table 2.6. Statistical summary related to Fig 2.11D and Fig 2.11I. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way... 51

Table 2.7. Statistical summary related to Fig 2.7 52

List of Figures

Figure 2.1. Acute therapeutic STN stimulation reduces PAC in the resting state. Representative example of PAC observed in M1 of a Parkinson's disease patient before (left), during (middle)... 14

Figure 2.2. Risk factors for the development of Parkinson's disease. Results of epidemiological studies have revealed various environmental exposures that increase (OR＞1) or decrease (OR＜1)... 15

Figure 2.3. Flexible graphene electrode array and treatment of epilepsy. (a) Schematic of a graphene-based seizure sensor. (b) Optical images of a epilepsy treatment sensor on a tube. (c)... 16

Figure 2.4. Graphene-based microelectrode array for brain mapping on the cortical surface. (a) Schematic illustration of the graphene-based electrode array. (b) Optical image of the device on... 18

Figure 2.5. Wireless edge computing neuroprosthetic device implementation (A) Schematic showing wirelessly controlled microprocessor connection to 32 channel graphene electrode for... 26

Figure 2.6. Strategies for correcting the behavior and brain waves of freely living hemi-parkinsonian rats through wireless cortical recording and stimulation. (A) Graphene electrode... 28

Figure 2.7. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats improves motor function. (A) Overview of the timeline of the experiment. (B) A schematic showing the... 32

Figure 2.8. Cylinder test after apomorphine administration to assure a PD motor symptom. (A) Schematic illustrating contralateral rotation in 6-OHDA-intoxicated PD rats after apomorphine... 33

Figure 2.9. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats decreases high-frequency brain waves and increases low-frequency brain waves. (A) Representative... 35

Figure 2.10. Categorization of brainwave modification according to different parts (fore arm, hind arm and face) after applying 130 Hz cortical stimulation in PD rats. Data are presented as... 36

Figure 2.11. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats enhances mGluR-mediated, long-term synaptic plasticity. (A) Schematic illustration of electrode location... 40

Figure 2.12. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats alters gene expression in the glutamatergic synapse pathway. (A) A heatmap illustrating the top 7... 42

Figure 2.13. Schematic illustration showing a circuit mechanism of how graphene stimulation implanted on the motor cortex can alleviate PD symptoms. The therapeutic effect of graphene... 45

초록보기

 파킨슨병은 두 번째로 흔한 신경퇴행성 질환으로, 주로 도파민 세포의 퇴화로 인해 발생합니다. 과거에는 다양한 의료 기기를 사용한 전자 치료 효과가 생체 조건, 무선 제어, 진단/치료 효과, 탈착형 인터페이스, 또는 뇌 질환 치료를 위한 생체 적합한 재료와 별도로 테스트되었습니다. 여기서는 우리의 그래핀 전극 어레이 기반 신경 이식물을 사용하여 무게동물의 운동 기능을 향상시키기 위해 대뇌 표면 자극을 사용했습니다. 이 시스템은 생체 적합성, 유연성, 탈착 가능성, 특정 대상, 그리고 무선 제어를 보여주는 최초의 통합 시스템입니다. 운동 피질 표면의 전자 자극은 운동 피질만을 활성화시켜 적은 부작용으로 치료 효과를 극대화했으며 동시에 운동 활동을 기록했습니다. 대뇌 피질의 자극은 운동 기능을 정상화시키고, 강화된 시냅스 응답에서 비롯된 파킨슨병 관련 뇌파를 교정했습니다. 이러한 변화는 글루타메이트 신경전달로인한 경로에서 metabotropic glutamate receptor (mGluR) (Grm5) 및 D5 도파민 수용체 (Drd5) 와 관련이 있었습니다. 무선 신경 이식물은 파킨슨병 및 다른 신경퇴행성 질환 환자를 대상으로 하는 생체 외 장치에 대한 폐쇠형 루프 시스템으로 잠재적인 진단 및 치료 기능을 보여주었습니다.

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