| Acknowledgements | 第8-15页 |
| List of Abbreviations | 第15-18页 |
| Abstract | 第18-22页 |
| 概要 | 第23-27页 |
| Chapter 1 The cerebral stroke induces nitrosative stress and caused neurovascular damage | 第27-34页 |
| 1.1 Introduction | 第28页 |
| 1.2 Role of calcium in excitotoxicity and ischemia | 第28-29页 |
| 1.3 The significance of calpains in strokes | 第29页 |
| 1.4 Nitrosative stress and BBB breakdown during ischemia | 第29-31页 |
| References | 第31-34页 |
| Chapter 2 Salvianolic acid A inhibits calpain activation and eNOS uncoupling during focal cerebral ischemia in mice | 第34-53页 |
| 2.1 Introduction | 第35-36页 |
| 2.2 Materials and Methods | 第36-40页 |
| 2.2.1 Experimental animals | 第36页 |
| 2.2.2 Extraction and Isolation of SAA | 第36页 |
| 2.2.3 Drug administration and transit middle cerebral artery occlusion mice model | 第36-37页 |
| 2.2.4 Neurologic evaluation | 第37页 |
| 2.2.5 Nissl Staining to assess infarct volume | 第37页 |
| 2.2.6 Immunoblotting analysis | 第37-38页 |
| 2.2.7 ~(18)F-FDG- micro-PET/CT Images and Quantitative Analysis | 第38-39页 |
| 2.2.8 Statistical analysis | 第39-40页 |
| 2.3 RESULTS | 第40-45页 |
| 2.3.1 SAA Ameliorated neurological dysfunctions and reduced brain infarction at 24 h after reperfusion | 第40-41页 |
| 2.3.2 Effects of SAA on Brain Glucose Metabolism | 第41-42页 |
| 2.3.3 SAA inhibited calpain activation in middle cerebral artery occlusion | 第42-43页 |
| 2.3.4 SAA attenuates the ischemia-induced eNOS uncoupling and inhibited peroxynitrite formation | 第43页 |
| 2.3.5 SAA prevents the dephosphorylation of AKT, ERK, and FKHR | 第43-45页 |
| 2.4 Discussion | 第45-47页 |
| 2.5 Summary | 第47页 |
| References | 第47-53页 |
| Chapter 3 Distribution of nitrotyrosine antibody conjugated PEG-LNs in ischemic brain | 第53-63页 |
| 3.1 Background | 第54页 |
| 3.2 Materials and methods | 第54-56页 |
| 3.2.1 Chemicals | 第54-55页 |
| 3.2.2 Preparation of β-carotene loaded PLNs | 第55页 |
| 3.2.3 Preparation of β-carotene loaded PLNs with antibody | 第55-56页 |
| 3.3 Characterization of lipid nanoparticles | 第56-57页 |
| 3.3.1 Size, zeta potential, and morphology measurements | 第56页 |
| 3.3.2 Drug encapsulation efficiency and drug loading content | 第56页 |
| 3.3.3 In vitro β-carotene release from lipid nanoparticles | 第56-57页 |
| 3.3.4 Statistics | 第57页 |
| 3.4 Results | 第57-59页 |
| 3.4.1 β-carotene encapsulation efficiency and drug loading content in PLNs with or without antibody | 第57-58页 |
| 3.4.2 Distribution of NT conjugated PEG-LNs in ischemic brain | 第58-59页 |
| 3.5 Discussion | 第59-60页 |
| 3.6 Summary | 第60页 |
| References | 第60-63页 |
| Chapter 4 Therapeutic effect of drug-loaded nitrotyrosine/PEG-Nanoconjugate against brain ischemic injury | 第63-81页 |
| 4.1 Background | 第64-65页 |
| 4.2 Materials and methods | 第65-68页 |
| 4.2.1 Experimental animals | 第65页 |
| 4.2.2 Transient cerebral ischemia model in mice | 第65-66页 |
| 4.2.3 Treatment groups and drug administration | 第66页 |
| 4.2.4 Western blotting | 第66-67页 |
| 4.2.5 Detection of Peroxynitrite generation | 第67页 |
| 4.2.6 Evaluation of BBB Damage | 第67页 |
| 4.2.7 Statistics | 第67-68页 |
| 4.3 Results | 第68-76页 |
| 4.3.1 Effects of BC emulsion, BC-PLNs and BC-NT/PLNs on neurological deficit and infarct size | 第68-69页 |
| 4.3.2 Neuroprotective effects of BC emulsion in mice model of tMCAO | 第69-71页 |
| 4.3.3 BC encapsulated NT/PLNs in reduced dose prevent the spectrin and calcineurin breakdown during brain ischemia | 第71-73页 |
| 4.3.4 BC encapsulated NT/PEG-nanoconjugate reduced dephosphorylation of AKT, FKHR, and ERK | 第73-74页 |
| 4.3.5 Inhibitory effect of BC encapsulated NT/PEG-nanoconjugate on peroxynitrite generation | 第74-76页 |
| 4.4 Discussion | 第76-77页 |
| 4.5 Summary | 第77-78页 |
| References | 第78-81页 |
| Chapter 5 Conclusions and future prospects | 第81-86页 |
| 5.1 Conclusions | 第82-84页 |
| 5.2 Future prospects | 第84-86页 |
| Author biography | 第86页 |
| Author Introduction | 第86页 |
| Honors and Awards | 第86页 |
| Publications | 第86页 |
