Neuroprotective Therapy for Stroke and Ischemic Disease 1st Edition by Paul Lapchak, John Zhang 3319453453 9783319453453

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ISBN-10 :  3319453453 

ISBN-13 : 9783319453453

Author:  Paul A. Lapchak, John H. Zhang 

A critical and comprehensive look at current state-of-the-art scientific and translational research being conducted internationally, in academia and industry, to address new ways to provide effective treatment to victims of ischemic and hemorrhagic stroke and other ischemic diseases. Currently stroke can be successfully treated through the administration of a thrombolytic, but the therapeutic window is short and many patients are not able to receive treatment. Only about 30% of patients are “cured” by available treatments. In 5 sections, the proposed volume will explore historical and novel neuroprotection mechanisms and targets, new and combination therapies, as well as clinical trial design for some of the recent bench-side research.

Neuroprotective Therapy for Stroke and Ischemic Disease 1st Table of contents:

Part I: Stroke Neuroprotection: The History and Learning Experience
Chapter 1: Reflections on Neuroprotection Research and the Path Toward Clinical Success
1 Introduction: A Brief Chronological History of Stroke
1.1 Of Neurons and Time
1.1.1 Extrapolated Stroke and Cerebrovascular Disease Incidence
1.1.2 Time–brain matters!
2 Limited Benefit Treatment Options for Acute Ischemic Stroke Victims: Successes!
2.1 Thrombolysis: Thrombolytic Therapy
2.2 Endovascular Procedures and Thrombolysis
2.2.1 ESCAPE [32]: Table 1.3
2.2.2 EXTEND-IA [33]: Table 1.4
2.2.3 MR CLEAN [31]: Table 1.5
2.2.4 REVASCAT [34]: Table 1.6
2.2.5 SWIFT-PRIME [35]: Table 1.7
2.2.6 Endovascular Procedure Benefit
2.3 Embolectomy Concerns
2.3.1 Patient Population Selection for Embolectomy and Thrombolysis
2.3.2 Limitations of the Trials
Patient Selection Bias
Saving Penumbra
Time to Treatment
Coadministration of Thrombolytics
2.3.3 Future of Embolectomy
Endovascular Procedure Summary
3 Neuroprotection
3.1 Evolving Opportunities
3.2 The RIGORs of Drug Development: Guideline Adherence
3.3 Meta-analysis of Translational Studies
4 Comorbidities and Models
4.1 Hypertension Models
4.2 Diabetic Models
4.2.1 Coadministration of Drugs in Stroke Models
5 Drug Development Considerations
6 Conclusion
References
Chapter 2: Systematic Review and Meta-analysis: Important Tools in Understanding Drug Development
1 Introduction
2 Evidence-Based Approaches to Understanding Translational Stroke Research
2.1 Assessing the Quality and Range of Available Evidence
2.1.1 Quality of Evidence
2.1.2 Range of Evidence
2.2 Assessing for Publication Bias
2.3 Impacts of Systematic Reviews
2.4 Providing Potential Explanations for Discrepancies Between Preclinical and Clinical Trial Res
2.5 Informing Clinical Trial Design
3 Limitations of Systematic Review and Meta-analysis
4 Future of Preclinical Systematic Review and Meta-analysis
5 Conclusions
6 Resources
References
Chapter 3: Neuroprotection Is Technology, Not Science
1 Introduction
2 Part 1: Physics and Biology
2.1 A Tale of Two Cultures
2.2 What Is Measured?
2.3 The Mathematizing of Biology
3 Part 2: A Theory of Acute Cell Injury
3.1 Introduction to the Theory
3.2 Qualitative Description of the Theory
3.3 The Autonomous Theory
3.4 Solutions of the Autonomous Theory
3.5 Monostable Outcome
3.6 Bistable Outcome
3.7 Pre-treatment Therapies
3.8 Closed Trajectories and the Autonomous Theory
4 Technological Applications
4.1 Approaches to Therapy
4.2 Ascertaining Injury Intensity
4.3 Protective Therapeutics
4.4 The Non-autonomous Dynamical Theory of Acute Cell Injury
4.5 Sequential Injuries
4.6 Solutions of the Multiple Injury Model
4.6.1 Preconditioning
4.6.2 Post-injury Drug Treatment
4.7 Spatial Applications
4.8 A Possible Neuroprotective Technology
5 The Mathematical Road to Neuroprotection
References
Chapter 4: History of Experimental Stroke Research
1 Introduction
2 Etymology, Origins, and Evolution of the Term Stroke
3 Conclusion
References
Chapter 5: History of Neuroprotection: Trials and Tribulations
1 Introduction
2 Cerebrovascular Ischemia Cascade
3 Drug Targets
3.1 Calcium Channel Blocker: Nimodipine
3.2 Glutamate Antagonists
3.3 Gamma-Aminobutyric acid (GABA) Agonists
3.4 Antioxidants
3.5 A Phospholipid Precursor: Citicoline
3.6 A Nitric Oxide Signal Transduction Modulator: Lubeluzole
3.7 Albumin
3.8 Hyperbaric Oxygen
3.9 Neurotrophic Factors
3.10 Modulation of Inflammation: Inhibition of Leukocytes
3.11 Hemodilution
3.12 Hypothermia
3.13 Magnesium
4 Reasons for Failure: Pre-clinical Experimental Studies
5 Reasons for Failure: Clinical Trials
6 Future Directions and Lessons Learned
References
Part II: Novel Neuroprotection Mechanisms and Targets
Chapter 6: Targeting PSD-95 as a Novel Approach in the Treatment of Stroke
1 Introduction
1.1 PSD-95/nNOS/NMDA Receptor Signaling Complex
1.1.1 NMDA Receptors
1.1.2 PSD-95
1.1.3 nNOS and NO Production
2 PSD-95 as Drug Target
2.1 Neuroprotective PSD-95 Inhibitors: NA-1
2.2 Multimeric Ligands Targeting PSD-95
2.3 Peptidomimetics Targeting PSD-95
2.4 Small Molecules Targeting the NMDA Receptor/nNOS/PSD-95 Complex
2.4.1 IC87201
2.4.2 ZL006
2.4.3 Tramiprosate
2.4.4 4-Phenyl-1-(4-Phenylbutyl)-Piperidine
2.4.5 Honokiol
3 Conclusion and Outlook
References
Chapter 7: ATP-Sensitive Potassium Channels (KATP) Play a Role in Hypoxic Preconditioning Against
1 Introduction
2 Classification and Structures of KATP Channels
2.1 Kir6.1 and Kir 6.2 Subunits
2.2 SUR 1 and SUR 2 Subunits
3 Gating, Regulation, and Pharmacology of KATP Channels
3.1 Gating
3.2 Regulation by Nucleotides, ATP and Mg-ADP
3.3 Pharmacological Properties
3.4 Non-nucleotide Cellular Regulation
4 Distribution of Neuronal KATP Channels
5 The Roles of Neuronal KATP Channel Under Physiological Conditions
6 Neuroprotective Role of KATP Channels in Cerebral Ischemia
7 KATP Channels in Preconditioning in Cerebral Ischemia or Hypoxic-Ischemic Brain Injury
7.1 Ischemic or Hypoxic Preconditioning
7.2 KATP Channels in Hypoxic Preconditioning-Induced Neuroprotection
8 Conclusion
References
Chapter 8: Targeting Oxidative Stress in Stroke
1 Oxidative Stress
1.1 Introduction
1.2 Chemistry of Oxidative Stress
1.3 ROS Sources
1.4 The Antioxidant System
2 Harmful Effects of Oxidative Stress
2.1 ROS/RNS Reactivity
2.2 Susceptibility of Macromolecules
2.3 Cell Death Mechanisms
3 Ischaemic Stroke and Oxidative Stress
3.1 The Ischaemic Cascade
3.2 Ischaemia and ROS
3.3 Ischaemia and RNS
3.4 Brain Damage
4 Stroke Treatment and Drug Discovery
4.1 Reperfusion
4.2 Past Failures
4.3 New Development
5 Targeting Oxidative Stress in Stroke: Strategies and Examples
5.1 Strategy 1
5.2 Strategy 2
5.3 Strategy 3
5.4 PSD-95
5.5 NADPH Oxidase
5.6 Keap1
6 Multi-target Drug Discovery
7 Conclusion and Perspectives
References
Chapter 9: Nitrones, Old Fellows for New Therapies in Ischemic Stroke
1 Introduction
2 Ischemic and Reperfusion Damage
2.1 Damage During Ischemia
2.2 Reperfusion Damage and Other Long-Term Contributions: Oxidative Stress
2.2.1 Lipid Peroxidation
2.2.2 Apoptosis
2.2.3 Reperfusion Contribution to Inflammation
2.3 Induced Reperfusion as Therapy for Stroke Treatment
3 Neuroprotection: Nitrones as Promising Drug Candidates
3.1 Nitrones as Antioxidant Agents and Spin Traps Deserve Special Attention
3.2 NXY-059 as the Furthest-Reaching Nitrone-Derived Drug Candidate to Date
3.3 Current Development of Nitrones
4 New Nitrones
4.1 In Vitro Tests for Antioxidant Effects
4.2 Neuroprotective Properties of Nitrones in Neuronal Cultures and in Animal Model of Transien
5 Nitrones Pleiotropy: New Perspectives
5.1 In Silico Target Identification for Nitrones
5.2 Exploring Nitrone-Based Multidrug Therapy
6 Conclusions
References
Chapter 10: Neuroprotective Strategies via Modulation of Innate Immune Receptors
1 Danger Theory and General Concept of Danger Signals (DAMPs)
2 Types of Innate Immune Receptors (PRRs)
3 Mechanisms of PRR Activation Under Ischemic Conditions
4 Modulation of PRRs in Stroke or Ischemia
References
Chapter 11: Harnessing the Power of the Human Immune System via Multi-omic Immune Profiling in S
1 Introduction
2 Profiling the Multi-omic Stroke Response and the Complexity of the Immune System
3 Leveraging Multi-omic Responses to Aid Stroke Diagnosis, Treatment, and Recovery
3.1 Stroke diagnosis
3.2 Stroke Treatment and Recovery
4 Future Opportunities
5 Conclusions/Summary
References
Chapter 12: Polarization of Microglia/Macrophages in Brain Ischaemia: Relevance for Stroke Therap
1 Introduction
2 The Innate Immunological Response of the Brain to Stroke
2.1 Blood-Borne Myeloid Cells
2.2 Differentiating Brain Resident Microglia from Blood-­Borne Macrophages
3 Polarization of Monocyte- or Microglia-Derived Macrophages in Stroke
4 Modulation of Microglia/Macrophages by microRNAs
5 Conclusions
References
Chapter 13: Endoplasmic Reticulum Stress: An Opportunity for Neuroprotective Strategies After Stro
1 The ER Structure and Functions
1.1 General Information
1.1.1 Chaperones of the Hsp70 (Heat Shock Protein 70) Family
1.1.2 Grp94
1.1.3 Calnexin/Calreticulin
1.1.4 IP3R (INOSITOL-1,4,5-Trisphosphate Receptor) Channels
1.1.5 RyR Channels (Ryanodine Receptor)
1.2 The ER in Neurones
2 The ER Stress Response/The UPR
2.1 Origin of ER Stress Activation
2.2 PERK Pathway
2.2.1 Translational Response Mediated by PERK
2.2.2 Transcriptional Response Mediated by PERK
2.3 ATF6 Pathway
2.4 IRE1 Pathway
2.5 UPR: Friend or Foe?
3 ER Stress and Stroke
4 ER Stress and Other Ischaemic Diseases
4.1 Cardiac Ischaemia
4.2 Renal Ischaemia
5 ER Stress and Neuroprotection in Ischaemic Diseases
5.1 Through UPR Pathways
5.2 Through Chaperones
5.3 Through Other Cell Death Pathways
6 Conclusion
References
Chapter 14: Effects of Neuroprotectants Before and After Stroke: Statins and Anti-hypertensives
1 Introduction
2 Statins
2.1 Hypercholesterolaemia as a Risk Factor for AIS
2.2 Pharmacology and Pharmacokinetics of Statins
2.3 The Pleiotropic Effects of Statins
2.4 Statins and Primary AIS Prevention
2.5 Statins and Primary Prevention in AIS Patients Treated with Thrombolysis
2.6 Statins and Secondary Prevention of Recurrent Stroke
2.7 Statins and Secondary Prevention in AIS Patients Treated with Thrombolysis
2.8 Conclusions
3 Anti-hypertensives
3.1 Hypertension as a Risk Factor for AIS
3.2 The Mechanism of Action of Anti-hypertensives and Their Pleiotropic Effects
3.2.1 ACE-Is and ARBs
3.2.2 Calcium Channel Blockers
3.2.3 Sympatholytics
3.2.4 Diuretics
3.3 Primary AIS Prevention
3.3.1 ACE-Is and ARBs
3.3.2 Calcium Channel Blockers
3.3.3 Sympatholytics
3.3.4 Diuretics
3.4 Primary Prevention in AIS Patients and Interaction with Thrombolysis
3.5 Secondary Prevention of Recurrent Stroke
3.6 Secondary Prevention in AIS Patients Treated with Thrombolysis
3.7 Conclusions
References
Chapter 15: Toward Effective Combination Therapy and Pleiotropic Drugs
1 Introduction
2 Adequate Reperfusion Is a Major Target for Neuroprotection
3 Uric Acid, a Powerful Antioxidant in Humans
4 Uric Acid Administration as a Neuroprotectant Drug
5 Concluding Remarks: Towards an Effective Combined Approach
References
Chapter 16: TRPM7 Channels as Potential Therapeutic Targets for Stroke
1 Introduction
2 Classification, Structures, and Distributions
2.1 Classification
2.2 Gene and Protein Structures
2.3 Tissue and Cellular Distribution
3 Biophysical Properties, Regulatory Mechanisms, Pharmacology
3.1 Biophysical Properties
3.2 Regulatory Mechanisms
3.3 Pharmacological Properties
4 Physiological Functions
5 Pathophysiological Relevance in Cerebral Ischemia and Hypoxia
6 Clinical Potentials and Therapeutic Perspectives
7 Conclusions
References
Chapter 17: Cholinergic Protection in Ischemic Brain Injury
1 Protection of Neuroprotection
2 Converting Nonneuronal Cells to Neurons
3 Therapeutics of Choline and Choline Derivatives
3.1 Biosynthesis of Phosphatidylcholine and Tissue Repair
3.2 Neuroprotective and Anti-inflammatory Efficacies of α7 nAChRs
3.3 Therapeutic Efficacy of Positive Allosteric Modulators
4 Possible Mechanisms of α7 nAChR Protective Action
5 Conclusions
References
Chapter 18: Remote Ischemic Conditioning: A Highly Translatable Therapy for Acute Stroke
1 Introduction
2 History of Preconditioning
3 History of the Concept of Ischemic Preconditioning and Remote Ischemic Conditioning
4 Mechanisms of RIC
4.1 Neural Mechanism
4.2 Humoral Mechanism
4.3 Nitric Oxide
4.4 Combined Neural and Humoral Mechanism
4.5 Systemic Anti-inflammatory Response
5 Remote Ischemic Conditioning in Acute Myocardial Infarction
6 Review of Preclinical Studies of RIC in Stroke
7 RIC and Cerebral Blood Flow
8 Clinical Trials of RIC in Acute Ischemic Stroke
9 Other Clinical Trials of RIC in Stroke
10 Future Directions and Conclusions
References
Chapter 19: Hypothermia for Acute Ischemic Stroke
1 Therapeutic Hypothermia and Its First Historical Applications
2 Extrapolation from Cardiac Arrest Population
3 The Pathophysiology of Stroke and the Effect of Hypothermia
3.1 Cerebral Metabolism
3.2 ATP Depletion, Ca2+ Influx, and the Release of Excitatory Neurotransmitters
3.3 Free-Radical Production
3.3.1 Inflammation
3.4 Apoptosis
4 Definitions
4.1 Levels of Hypothermia
4.2 Phases of Temperature Modulation
5 Methods of Temperature Modulation
5.1 Pharmacologic Interventions
5.2 Surface Cooling
5.3 Intravascular Cooling
5.4 Selective Cooling
6 Adverse Events Associated with Therapeutic Hypothermia
6.1 Shivering
6.2 Cardiac and Hemodynamic Complications
6.3 Metabolic Panel Abnormalities
6.4 Infectious Risks
6.5 Coagulopathy and Bleeding Risk
7 Preclinical Data
8 A Review of Clinical Trials for Therapeutic Hypothermia in the Treatment of Acute Ischemic St
8.1 Early Clinical Feasibility and Safety Trials
8.2 The Introduction of Modern Cooling Devices for Induction
8.3 Induced Hypothermia in Combination with Systemic Thrombolytic Therapy
8.4 Induced Hypothermia in Combination to Decompressive Hemicraniectomy
8.5 Induced Hypothermia in Combination with Intra-arterial Treatment
8.6 Phase III Trials for Therapeutic Hypothermia
9 Conclusion
References
Chapter 20: Modern Endovascular Treatment of Ischemic Disease
1 Introduction
2 Medical Thrombolysis in Stroke
3 Initial Approaches to Endovascular Stroke Treatment
4 Early Endovascular Trials
5 Rapid Advancement of Endovascular Technology
6 Early Randomized Controlled Trials of Stroke Intervention
7 Breakthrough of Modern Mechanical Thrombectomy Devices
8 Current Standard of Care
9 Directions for Future Research and Clinical Guidelines
10 Conclusions
References
Chapter 21: Cerebral Microbleeds and Thrombolysis for Acute Ischemic Stroke
1 Introduction
2 Radiographic Characteristics of Cerebral Microbleeds
2.1 Cerebral Microbleeds and Cerebral Microhemorrhage
2.2 Postthrombolysis Intracerebral Hemorrhage
2.3 Cerebral Small Vessel Disease and Postthrombolysis Intracerebral Hemorrhage
2.4 Cerebral Microbleeds and Postthrombolysis Intracerebral Hemorrhage
3 Conclusions
References
Chapter 22: Targeting Pericytes and the Microcirculation for Ischemic Stroke Therapy
1 Introduction
2 Hemodynamic Effects of Stroke
3 Hemodynamic Effects of Recanalization
4 Capillary Blood Flow
5 Pericytes as Regulators of Capillary Blood Flow
6 Microvascular Changes in Stroke
7 No-Reflow as a Therapeutic Target
8 Conclusion
References
Part III: Thrombolysis and Embolectomy
Chapter 23: Thrombolytic and Endovascular Therapies for Acute Ischemic Stroke
1 Thrombolytic Therapy in Acute Stroke
1.1 Streptokinase
1.2 Urokinase and Prourokinase
1.2.1 Urokinase
1.2.2 Prourokinase
1.2.3 Desmoteplase
1.3 Tissue Plasminogen Activator
1.3.1 Treatment up to 3 h After Symptom Onset
1.3.2 Treatment Later than 3 h from Symptom Onset
1.3.3 Controversies Surrounding tPA Treatment of Ischemic Stroke
1.4 Future Directions for IV tPA Treatment of Ischemic Stroke
2 Endovascular Treatment in Acute Stroke
2.1 Fundamentals of Catheter-Based Angiography
2.2 Intraarterial Thrombolysis
2.3 First-Generation Mechanical Thrombectomy Devices
2.3.1 Merci Device
2.3.2 Penumbra Device
2.3.3 EKOS Catheter System
2.4 Development of Reperfusion Scales
2.5 Second-Generation Mechanical Thrombectomy Devices
2.5.1 Solitaire FR Device
2.5.2 Trevo Device
2.5.3 Direct Aspiration Catheters
2.6 First-Generation Randomized Controlled Studies
2.6.1 International Management of Stroke 3 Trial
2.6.2 MR RESCUE
2.7 Development of Imaging Criteria for Patient Selection
2.7.1 ASPECTS Score
2.7.2 CT Angiogram Collateral Scores
2.7.3 Perfusion Imaging
2.8 Acute Ischemic Stroke Therapies 2015: The Next Generation of Randomized Data
2.8.1 MR CLEAN
2.8.2 REVASCAT
2.8.3 ESCAPE
2.8.4 SWIFT PRIME
2.8.5 EXTEND-IA
2.9 Why Did Thrombectomy Work in 2015 and not 2013?
References
Chapter 24: Sonothrombolysis for Acute Ischemic Stroke: A Critical Appraisal
1 Introduction
2 Definitions and Mechanisms
2.1 Technical Issues
2.2 Physiology
3 Clinical Trials
3.1 Sonothrombolysis
3.2 Microsphere-Potentiated Sonothrombolysis
3.3 Sonolysis
3.4 Intraarterial Sonothrombolysis
3.5 Meta-analyses
4 Pitfalls and Future Directions
References
Chapter 25: Combination Therapy with Thrombolysis
1 Introduction
2 The Rationale for a tPA Combination Therapy
3 Drugs with Anti-inflammatory Activity
4 Drugs Targeting Glutamate Toxicity
5 Drugs with Free Radical Scavenging Activity
5.1 The Role of Uric Acid and tPA Combination in Cerebral Ischemia
5.2 The Role of 17B-Estradiol and tPA Combination in Cerebral Ischemia
5.3 The Role of Edaravone and Melatonin in Combination with tPA
5.4 The Role of tPA Receptor Blockage in Cerebral Ischemia
6 Drugs Targeting RHO Kinases
7 Proteasome Inhibitors
8 Growth Factors
9 Nonpharmacological Approaches
10 Translational Aspects
11 Conclusion
References
Chapter 26: Oxygen Carriers: Are They Enough for Cellular Support?
1 Introduction
2 Hemoglobin-Based CSMs (HB-CSMs)
3 Perfluorocarbon-Based CSMs (PFCB-CSMs)
4 Heme-Nitric Oxide/Oxygen Based CSMs (H-NOXB-CSMs)
5 The FDA
6 Addressing More than Carrying Oxygen
References
Chapter 27: A New Paradigm in Protecting Ischemic Brain: Preserving the Neurovascular Unit Before
1 Therapeutic Target: Salvaging At-Risk Cerebral Tissue
1.1 Evolution of the Penumbra
1.2 Recanalized Patients: Is There Any Brain Tissue Left to Save?
2 Adjunctive Therapeutic Approaches: Tissue Protection and Recanalization
2.1 From Neuroprotection to Cytoprotection
2.2 Promising Cytoprotective Approaches
3 Oxygen Delivery in Ischemic Disorders: Preclinical Success and Clinical Failures
3.1 HBO-NBO: Preclinical Promise and Clinical Failure of Inhaled Oxygen Therapies
3.1.1 Preclinical Studies with HBO and NBO
3.1.2 Failure to Translate HBO and NBO into Clinical Success
3.2 HBOCs/PFCs: Preclinical Promise and Clinical Safety Issues of Artificial Oxygen Carriers
3.3 Applying Lessons Learned to New Oxygen Carriers
4 OMX Oxygen Carrier: Features and Preclinical Promise
4.1 H-NOX Technology
4.2 OMX Mechanism
4.3 OMX Safety Profile in Preclinical Testing
5 Challenges and Opportunities in Combined Trials of Thrombolytic or Endovascular Therapies
5.1 Challenges in Adjunctive Therapy Trials
5.2 Opportunities in Prehospital Treatment
6 Conclusions
References
Part IV: Stroke Models and Clinical Trial Considerations
Chapter 28: The Right Rodent for the Job: Infarct Variability Between Strains and Its Impact on 
1 Introduction
2 Influence of Inclusion Criteria on Infarct Volume Variability in Sprague-Dawley Rats
3 Comparison of Variability in Infarct Volume Across Different Strains of Rat
4 Discussion
5 Methods
References
Chapter 29: Rabbit Spinal Cord Ischemia Model for the Development of Neuroprotective Treatments
1 Introduction
2 Potential Therapeutic Agents
3 Animal Models of Spinal Cord Injury
4 Minimally Invasive Rabbit Spinal Cord Ischemia Model
4.1 Methods
4.2 Results
5 Discussion
6 Conclusion
References
Chapter 30: Stroke Sex Differences: From Basic Research to Clinical Trials
1 Introduction
2 Stroke Incidence, Symptoms and Outcome
3 Sex and Stroke: Hormones and Intrinsic Factors
4 Mechanisms of Injury
5 Sex Differences in Treatment: Clinical and Preclinical Studies
6 Future Directions
References
Chapter 31: Unpuzzling the Comorbid Type 2 Diabetes and Hypertension-Related Cognitive Dysfunction
1 Introduction
1.1 T2D, Hypertension, and the CNS
1.1.1 Hypertension and the Renin-Angiotensin-Aldosterone System
1.1.2 Hypertension and Oxidative Stress
1.1.3 Hypertension in CNS Disorders
Hypertension and AD
Hypertension, T2D, and Stroke
1.2 The Promising Potential of Antihypertensive Drugs Against CNS Damage Caused by Hypertension C
1.2.1 ARBs
1.2.2 ACEi
2 Conclusions
References
Chapter 32: Sex-Specific Factors in Stroke
1 Sex-Specific Risk Factors
1.1 Pregnancy
1.2 Hormones and Stroke Risk
2 Sex Differences in Primary Prevention
3 Sex Differences in Embolic Stroke
4 Sex Differences in Acute Stroke Management
5 Aging and Stroke
6 Sex Differences in Cerebral Blood Flow
7 Cell Death Mechanisms
8 Outcomes After Stroke
8.1 Social Isolation, Loneliness, and Stroke
8.2 Depression and Stroke
References
Chapter 33: Current Imaging Strategies for Patient Selection in Acute Ischemic Stroke Trials
1 CT-Based Imaging
1.1 Noncontrast CT and ASPECT Score
1.2 CT Angiogram
1.2.1 Multiphase CT Angiography
1.3 CT Perfusion Imaging
1.3.1 Technical Considerations in Using CT Perfusion
1.3.2 Optimal Parameters for Patient Selection
1.3.3 Thresholds and Performance of CTP Parameters
1.4 RAPID
2 MRI-Based Imaging
2.1 Diffusion-Weighted Imaging
2.1.1 Diffusion Lesion Evolution
2.2 MR Angiography
2.3 MR Perfusion-Weighted Imaging
2.3.1 The Malignant Profile
2.3.2 Arterial Spin Labeling (ASL)
2.4 The Role of MRI in Future Clinical Trials
3 Novel Neuroimaging Approaches for Patient Selection
3.1 Mobile Stroke Treatment Unit
3.2 Multimodal in-Suite Imaging
3.3 Quantitative Magnetic Resonance Angiography
4 Conclusion

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