創傷性腦損傷是一種常見的神經損傷，通常是受外部撞擊形成，容易導致大量細胞死亡，並引起患者在生理與心理上的問題，帶來嚴重的後果。創傷性腦損傷後的繼發性損傷容易導致傷口惡化，其中包括星形膠質細胞會誘導持續的神經炎症反應，導致神經元和血管功能障礙，而且會在傷口周圍積累形成疤痕，阻擋新生細胞的進入修復。除此之外，由於異物的入侵容易引發宿主自發的免疫反應，因此需要開發一種更為安全且有效的方法，在提供有效治療的同時減少免疫反應的發生。
研究中使用的GNP@PMNO是一種奈米藥物遞送系統，是通過將血小板膜（PM）和亞硝酸鈉（NaNO2）結合，組成接有NO基團的血小板膜（PMNO）後，再包覆在金納米顆粒（GNPs）上，組成具有血小板膜包覆的金奈米粒子（GNP@PMNO）。
在這項研究中，GNP@PMNO具有高度生物相容性和釋放控制能力。血小板膜的包覆使得這些奈米粒子具有優異的穿越血腦屏障的能力，同時保護了內部承載。在高頻磁場 (High Frequency Magnetic Field, HFMF) 環境下，系統中的GNPs 因其導體特性可以產生渦電流，而電場的改變可刺激神經細胞使其向外生長，促使腦神經的生長與修復。此外，GNPs在磁場的感應下，可以使PMNO中的S-NO鍵斷裂，從而釋放出一氧化氮氣體（NO）。NO作為一種神經傳遞物質，在TBI的治療中具有重要的生物學效應，包括促進神經細胞增生和突觸形成，減少神經炎症反應，以及保護神經元免受氧化損傷。
在材料方面，本實驗研究了不同大小的金奈米顆粒的產電量，且通過SEM,XRD,TGA等證明了PM能夠包覆到GNPs上，並通過Greiss reagent來驗證NO的釋放。在細胞實驗中，本研究證明了GNP以及PMNO對於 NIH-3T3 細胞具有低細胞毒性,也借由胚胎神經幹細胞（Neural Stem Cells, NSCs）的實驗，驗證了GNP@PMNO+HFMF的組別具有刺激神經幹細胞生長，增加神經分化比例的功能。在動物實驗中，治療7天后的腦切片可以觀察到，星狀膠質細胞的量相較於未治療的組別有顯著的下降，血管細胞也有相對提升，證明治療能減少傷口處免疫反應的發生，同時也能促進血管的再生。在動物行為測驗中，治療組的老鼠四肢的運用能力與靈活度都高於未治療組。有此可知，本實驗具有修復創傷性腦損傷的潛力，PM不僅具有高度的生物相容性，可以降低宿主的免疫反應，而且通過施加外部磁場能夠使GNPs的電場發生變化，搭配NO對神經的生長與修復能力，提供了一種對於創傷性腦損傷的有效治療方式。

Traumatic brain injury (TBI) is a common type of neural injury, often resulting from external impact, which can lead to significant cell death and cause physiological and psychological issues in patients, resulting in serious consequences. Secondary injuries following traumatic brain injury can exacerbate wound deterioration, including persistent neuroinflammatory reactions induced by astrocytes, leading to neuronal and vascular dysfunction, as well as the accumulation of scar tissue around the wound, hindering the entry of new cells for repair. In addition, since the invasion of foreign bodies can easily trigger a spontaneous immune response in the host, a safer and more effective method needs to be developed to provide effective treatment while reducing the occurrence of immune responses.
The GNP@PMNO utilized in the study is a nanoscale drug delivery system, formed by conjugating platelet membrane (PM) with sodium nitrite (NaNO2), resulting in platelet membrane (PM) with attached NO groups (PMNO), which is then encapsulated onto gold nanoparticles (GNPs), forming platelet membrane-coated gold nanospheres (GNP@PMNO).
In this study, GNP@PMNO exhibits high biocompatibility and release control capability. The encapsulation of platelet membrane endows these nanoparticles with excellent ability to traverse the blood-brain barrier while protecting the internal payload. In a High-Frequency Magnetic Field (HFMF) environment, GNPs in the system generate eddy currents due to their conductor properties, and changes in the electric field can stimulate nerve cells to grow outward, promoting brain neurogenesis and repair. Additionally, under the influence of the magnetic field, GNPs induce the cleavage of S-NO bonds in PMNO, thereby releasing nitric oxide gas (NO). NO, as a neurotransmitter, plays important biological roles in the treatment of TBI, including promoting neuronal proliferation and synaptic formation, reducing neuroinflammatory responses, and protecting neurons from oxidative damage.
In terms of materials, this experiment investigated the power generation of gold nanoparticles (GNPs) of different sizes. Through SEM, XRD, TGA, etc., it was demonstrated that platelet membrane (PM) could be encapsulated onto GNPs. The release of NO was verified using the Griess reagent. In cell experiments, this study demonstrated that GNP and PMNO had low cytotoxicity to NIH-3T3 cells. Additionally, experiments with embryonic neural stem cells (NSCs) validated the ability of the GNP@PMNO+HFMF group to stimulate NSC growth and increase the ratio of neural differentiation. In animal experiments, brain slices taken after 7 days of treatment showed a significant decrease in the number of astrocytes compared to the untreated group, along with a relative increase in vascular cells, indicating that the treatment could reduce the occurrence of immune reactions at the wound site and promote vascular regeneration. In behavioral tests on animals, the treated group of mice exhibited higher limb utilization and agility compared to the untreated group. Therefore, this experiment has the potential to repair traumatic brain injuries. PM not only exhibits high biocompatibility, reducing the host's immune response, but also, when combined with external magnetic fields, can induce changes in the electric field of GNPs. This, coupled with NO's ability to promote neural growth and repair, provides an effective treatment for traumatic brain injuries.

Table of Contents
中文摘要 2
Abstract 4
致謝 6
Table of Contents 7
List of Figure 9
Chapter 1 Introduction 13
Chapter 2 Literature review and theory 16
2.1 Traumatic Brain Injury 16
2.1.1 Secondary damage after TBI 18
2.1.2 Astrocytes in Traumatic Brain Injury 20
2.1.3 Microglia in Traumatic Brain Injury 22
2.2 Magneto-electric Stimulation 24
2.2.1 Electrical Stimulation (ES) and Neuron Modulation 24
2.2.2 Magneto-electric nanoparticles (MENPs) 27
2.2.3 Electro-magnetized gold nanoparticle 29
2.3 The role of nitric oxide in biologic 31
2.3.1 NO for Neuron Repair 32
2.3.2 NO for Wound Repair 34
2.4 Platelet coating 36
2.4.1 The role of platelets in biologic 38
2.4.2 Wound repairing of platelets 40
Chapter 3 Experimental Section 43
3.1 Materials 43
3.2 Apparatus 45
3.3 Methods 47
3.3.1 Synthesis of gold nanoparticles (GNPs) 47
3.3.2 Synthesis of platelet membrane-NO (PMNO) 47
3.3.3 NO release assay 48
3.3.4 In vitro cell culture 48
3.3.4.1 Cell viability assay 49
3.3.4.2 Cell uptakes 50
3.3.4.3 Embryonic NSCs extraction experiment 50
3.3.4.4 Differentiation of NSCs experiment 51
3.3.5 In vivo experiment 53
3.3.5.1 brain collection and immunofluorescence staining 54
3.3.5.2 Animal behavior experiment 55
Chapter 4 Results and Discussions 57
4.1 Characterization of material 57
4.1.1 Characterization of GNPs 57
4.1.2 Characterization of PMNOs 62
4.2 In vitro experiment 64
4.2.1 Cytotoxicity of materials 64
4.2.2 Cell uptakes 65
4.2.3 Stimulate neuron differentiation 67
4.3 In vivo experiment 71
4.3.1 In vivo degradation of GNP@PMNOs 71
4.3.2 Immunofluorescence staining and analysis 73
4.3.3 Animal behavior treatment 87
Chapter 5 Conclusion 90
Reference 92

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