Molecular, genetic, and cellular advances in cerebrovascular diseases

Description

Contents Preface 1. Imaging in Cerebrovascular Disease 1.1 Imaging of the Arterial and Venous Lumen 1.1.1 CT angiography (CTA/CTV ) 1.1.2 MR angiography (MRA/MRV ) 1.1.3 Catheter-based digital subtraction angiography 1.2 Dynamic Imaging of Blood Flow 1.3 Intracranial Vessel Wall Imaging 1.4 Imaging of Parenchymal Physiology 1.5 Anatomic Brain Imaging 1.6 Summary Acknowledgments References 2. Cell Mechanisms and Clinical Targets in Stroke 2.1 Neuroprotection 2.2 Reperfusion 2.3 Neurovascular Unit 2.4 Biphasic Penumbra 2.5 Cofactors and Comorbidities 2.6 Translational Opportunities 2.6.1 Stroke genetics 2.6.2 Remote conditioning 2.7 Summary References 3. Neural Repair for Cerebrovascular Diseases 3.1 Current Therapies 3.2 Spontaneous Recovery from Stroke 3.3 Therapies to Promote Neural Repair 3.3.1 Growth factors 3.3.2 Monoaminergic drugs 3.3.2.1 Dopamine 3.3.2.2 Serotonin 3.3.2.3 Norepinephrine 3.3.2.4 Other drugs 3.3.3 Traditional and alternative medicines 3.3.4 Cell-based therapies 3.3.5 Other therapies 3.3.6 Brain stimulation 3.4 Principles of Neural Repair After Stroke 3.4.1 Time-sensitive 3.4.2 Experience-dependent 3.4.3 Patient stratification 3.4.4 Modality-specific measures 3.4.5 Brain organization Acknowledgments References 4. Brain AVM: Current Treatments and Challenges 4.1 Management 4.1.1 Observation 4.1.2 Microsurgical resection 4.1.3 Stereotactic radiosurgery 4.1.4 Endovascular embolization 4.2 Challenges in the Treatment of Brain AVMs 4.2.1 Unruptured AVMs 4.2.2 High-grade AVMs References 5. Animal Models and Prospective Therapeutic Targets for Brain Arteriovenous Malformation 5.1 The Development of bAVM Models 5.1.1 Hemodynamic models 5.1.1.1 Carotid-jugular fistulae models 5.1.1.2 Rete mirabile models 5.1.2 Genetic models 5.1.2.1 Mutation of HHT causative genes 5.1.2.2 Zebrafish model 5.1.2.3 Mouse models 5.1.2.3.1 Alk1 or Eng knockout 5.1.2.3.2 Alk1 or Eng conditional knockout 5.1.2.3.3 Angiogenic stimulation 5.1.2.3.4 Adult onset bAVM mouse models 5.1.2.3.4.1 Brain focal Alk1 or Eng homozygous deletion plus angiogenic stimulation 5.1.2.3.4.2 Conditional deletion of Alk1 or Eng globally plus brain focal angiogenic stimulation 5.1.2.3.4.3 Endothelial Alk1 gene deletion plus brain angiogenic stimulation 5.1.2.3.5 Developmental models 5.1.2.4.6 SMAD4 mutation 5.1.2.3.7 Other genetic bAVM mouse models 5.1.2.3.7.1 Mutation of matrix Gla protein (Mgp) 5.1.2.3.7.2 Notch gain or loss of function 5.1.2.3.7.3 Rbpj mutation 5.1.2.3.8 Integrin b8 (Itgb8) mutant 5.1.3 Future models 5.2 Knowledge Gained from Animal Models Regarding AVM Pathogenesis 5.2.1 Molecular pathways 5.2.1.1 TGF 5.2.1.2 Notch 5.2.1.3 RASA1 5.2.2 Loss of function of the normal allele (2nd hit) 5.2.2.1 Modifier genes 5.2.2.2 Angiogenesis 5.2.2.3 Endothelial gene mutation 5.2.2.4 Vascular integrity 5.2.2.5 Inflammation and other environmental factors 5.2.2.6 BM-derived cells 5.2.3 Therapeutic development 5.2.3.1 Anti-angiogenesis 5.2.3.2 Anti-inflammation 5.2.3.3 Improvement of vascular integrity 5.2.3.4 Bone marrow or bone marrow-derived monocyte transfusion 5.2.3.5 Promising drugs not tested for bAVM 5.3 Summary Acknowledgments References 6. Biology of Brain Aneurysms 6.1 Histopathology of Normal Intracranial Arteries and Aneurysms 6.2 Aneurysm Pathogenesis 6.3 Macrophage Infiltration in Aneurysms 6.4 Matrix Metalloproteinases in Aneurysms 6.5 Mast Cells in Aneurysms 6.6 Pharmacologic Treatments Targeting Inflammation 6.6.1 Statins 6.6.2 Peroxisome proliferator-activated receptor gamma agonists 6.6.3 Renin–angiotensin system 6.7 Conclusion References 7. Intracranial Aneurysms: Imaging, Hemodynamics, and Remodeling 7.1 Origin and History of Intracranial Aneurysms 7.2 Treatment Options 7.3 Geometric Morphology of Intracranial Aneurysms 7.4 In vivo Imaging of the Lumen of Intracranial Aneurysms 7.5 In vivo Imaging of the Vessel Wall and the Velocity Field 7.6 Computational Fluid Dynamics 7.7 Image-based Monitoring of Cerebral Aneurysms 7.8 Relationship of Aneurysmal Changes to Hemodynamics 7.9 Summary Acknowledgments References 8. Recent Advances in CADASIL Research 8.1 Discovery 8.2 Epidemiology 8.3 Pathology and Pathogenesis 8.3.1 Unique features of genetic defects 8.3.2 Pathology 8.3.3 Pathogenesis 8.3.3.1 Cerebral vasculature dysfunction 8.3.3.2 Impaired N3ECD processing in VSMCs and ECs 8.3.3.3 GOM deposition and impaired biological functions 8.4 Clinical Syndromes and Neuroimaging Features 8.4.1 Clinical syndromes 8.4.1.1 Migraine with aura 8.4.1.2 Recurrent ischemic strokes 8.4.1.3 Mood disturbance and apathy 8.4.1.4 Cognitive impairment and dementia 8.4.2 Neuroimaging features 8.5 Treatment 8.6 Conclusion Acknowledgments References 9. Dural Fistula 9.1 Definition 9.2 Epidemiology 9.3 Anatomy 9.4 Pathophysiology 9.4.1 Anatomy 9.4.2 Hemodynamic 9.4.3 Basic science 9.4.4 Environmental factors 9.4.5 Summary: Pathophysiology 9.5 Natural History 9.5.1 Classification 9.5.2 Prognostic risk stratification; angioarchitecture 9.5.3 Prognostic risk stratification; clinical presentation 9.5.4 Prognostic risk stratification: clinical outcomes 9.5.5 Summary: Natural history 9.6 Clinical Presentation 9.6.1 Summary: Clinical presentation 9.7 Diagnosis 9.7.1 Overview 9.7.2 Computed tomography 9.7.3 Magnetic resonance 9.7.4 Adjuvant MR techniques 9.7.5 Digital subtraction angiography 9.7.6 Summary: Diagnosis 9.8 Treatment 9.8.1 Overview 9.8.2 Endovascular 9.8.3 Transarterial 9.8.4 Transvenous 9.9 Embolic Agents 9.10 Anatomic Considerations 9.11 Follow-up 9.12 Treatment 9.12.1 Surgery 9.12.2 Radiosurgery 9.12.3 Pediatric 9.12.4 Alternative therapies and research 9.13 Conclusion References 10. Interventional Therapies for Cerebrovascular Diseases 10.1 Acute Ischemic Stroke 10.2 Atherosclerotic Cerebrovascular Disease—Extracranial Carotid Disease 10.2.1 Management 10.2.1.1 Conservative 10.2.1.2 Surgical treatment 10.2.1.3 Carotid angioplasty and stenting 10.2.1.4 Evidence from the literature for carotid stenting 10.3 Arteriovenous Malformations 10.3.1 Natural history 10.3.2 Role of catheter angiography 10.3.3 AVM treatment 10.3.4 Embolic agents 10.3.5 Technique 10.4 Intracranial Aneurysms 10.4.1 Ruptured aneurysms 10.4.2 Unruptured aneurysms Acknowledgments References 11. Stem Cell-mediated Biobridge: Crossing the Great Divide Between Bench and Clinic in Translating Cell Therapy for Stroke 11.1 Benefits of Stem Cell Treatment in Stroke 11.2 Secondary Cell Death in Stroke as a Therapeutic Target for Stem Cell Transplantation 11.3 Inciting the Self-regenerative Mechanism in Stroke 11.4 Regenerative Medicine Circumvents the Restricted Therapeutic Window for Stroke 11.5 Stem Mobilization as Standalone and in Combination Therapy 11.5.1 Directing stem cells under the influence of drugs 11.5.2 Nourishing stem cells in a microenvironment favorable for regeneration 11.6 Multitude of Options, but Transplantable Stem Cells Need to be Identified 11.7 Safety of MSCs is Only Half the Story, with their Clinical Efficacy Unproven 11.8 Biobridge: Stem Cell-paved Path Between Endogenous Neurogenic Niche and Remote Injured Brain Areas 11.9 Translational Caveats of Biobridge Formation from Bench to Clinic 11.10 Outstanding Issues Relevant to Stem Cell Therapy in Stroke 11.11 Conclusion Acknowledgments References Index