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Reverse arteriogenesis with mechanical barrier disruption in experimental models of ischemic stroke

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dc.contributor.advisor홍, 지만-
dc.contributor.author박, 근화-
dc.date.accessioned2021-01-06T02:34:37Z-
dc.date.available2021-01-06T02:34:37Z-
dc.date.issued2020-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/19225-
dc.description.abstract비공개-
dc.description.tableofcontentsⅠ. INTRODUCTION 1
A. Ischemic stroke 1
1. Clinical significance of stroke 1
2. Pathophysiology of ischemic stroke 1
3. Current treatment of ischemic stroke 2
B. Moyamoya disease and syndrome 4
1. Epidemiology and clinical symptoms of MMD 4
2. Pathophysiology of MMD 5
3. Current treatment of MMD 6
C. Mechanical barrier disruption (MBD) 8
D. Crosstalk of focal inflammation and regional angiogenesis 10
E. Neovascularization 11
1. Vasculogenesis, angiogenesis, and arteriogenesis 11
2. Post-stroke angiogenesis 12
F. Erythropoietin as angiogenic boosters 14
G. Aims of this study 15
Ⅱ. MATERIALS AND METHODS 16
A. Ethics statement 16
B. Animal and general procedures 16
C. Animal models 16
D. Animal groups and drug administration 17
E. Mechnical barrier disruption (MBD) 18
F. Therapeutic hypothermia (TH) 18
G. Behavioral test 18
H. Measurement of hematocrit 19
I. In vivo brain imaging 19
1. Measurement of cerebral blood flow 19
2. Time-of-flight (TOF) magnetic resonance angiography (MRA) 19
J. Post-mortem microangiography 20
1. Black India ink 20
2. Blue dye injection 20
K. Blood-brain barrier (BBB) leakage analysis 21
L. TTC staining 21
M. Immunohistochemistry 21
N. Cresyl violet staining 22
O. Quantitative real time polymerase chain reaction (qRT-PCR) 22
P. Western blot 23
Q. In vitro experimental design 24
R. Tube formation of HUVECs 25
S. Wound healing of hAoSMCs 25
T. Statistical analysis 26
Ⅲ. RESULTS 31
PART A. Reverse arteriogenesis by MBD procedure in the mild ischemic rat model. 31
1. Establishment of mild ischemia model 31
2. MBD modulates extracranial and intracranial environments 33
3. MBD induce reverse arteriogenesis from extracranium 36
PART 2. The effect of cerebral inflammation on reverse arteriogenesis by MBD procedure in mild ischemic rat model 39
1. The effect of systemic inflammation by LPS treatment in the mild ischemic rat model 39
2. The effect of systemic inflammation in mild ischemic rat model with MBD procedure. 44
PART 3. The effect of erythropoietin pretreatment on reverse arteriogenesis by MBD procedure in mild ischemic rat model 50
1. EPO pretreatment enhance angiogenesis and arteriogenesis in MBD region 50
2. EPO pretreatment mitigated inflammation in MBD region 58
3. EPO stimulated Angiogenesis and arteriogenesis by regulating of TGF-β1 and MMP-2 64
4. Minocycline suppress the ability of EPO to induce vascular maturation 70
PART 4. The feasibility of MBD procedure in severe ischemic rat model 74
1. Establishment of severe ischemia model 74
2. Futility of combination therapy in severe ischemia model 82
3. Comparison of mild and severe ischemia model 86
4. Challenge for reverse arteriogenesis in severe ischemia model 92
Ⅳ. DISCUSSION 99
1. MBD-induced reverse arteriogenesis 99
2. Extracranial and intracranial angiogenic modulation by MBD procedure 100
3. Intracranial milieu modulation 102
1) Inflammation modulation. 102
2) Vessel maturation. 104
4. Reverse arteriogenesis in severe ischemia model 105
5. Intracranial and extracranial milieu modulation by combination therapy 106
Ⅴ. CONCLUSION 110
REFERENCES 111
CONTRIBUTIONS 126
국문요약 127		-
dc.language.isoen-
dc.titleReverse arteriogenesis with mechanical barrier disruption in experimental models of ischemic stroke-
dc.title.alternative허혈성 뇌졸중 실험 모델들에서 물리적장벽파괴술에 의한 역방향 혈관생성-
dc.typeThesis-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000029710-
dc.subject.keywordArteriogenesis-
dc.subject.keywordAngiogenesis-
dc.subject.keywordIschemic stroke-
dc.subject.keywordErythropoietin-
dc.subject.keywordcranial burr hole-
dc.subject.keywordMechanical barrier disruption-
dc.subject.keyword신생혈관생성-
dc.subject.keyword허혈성 뇌졸중-
dc.subject.keyword에리스로포이에틴-
dc.subject.keyword대뇌 천공술-
dc.subject.keyword물리적장벽파괴술-
dc.description.degreeDoctor-
dc.contributor.department대학원 의생명과학과-
dc.contributor.affiliatedAuthor박, 근화-
dc.date.awarded2020-
dc.type.localTheses-
dc.citation.date2020-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
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