Molecular, genetic, and cellular advances in cerebrovascular diseases

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