Regenerative Therapies in Ischemic Stroke Recovery

Foreword by Prof. P. K. Seth
Foreword by Prof. (Dr.) Sarman Singh
Contents
About the Editor
1: Targeting Adult Neurogenesis for Brain Recovery After Stroke: The Next Frontier in Stroke Medicine
	1.1 Introduction
	1.2 Adult Neurogenesis
	1.3 Techniques to Investigate Adult Neurogenesis
		1.3.1 Post-mortem/Histological Techniques
		1.3.2 In Vivo Techniques
	1.4 Evidence of Adult Neurogenesis After Stroke: Preclinical and Clinical
	1.5 Limitations Related to Endogenous Post-stroke Neurogenesis
	1.6 Strategies to Promote Post-stroke Neurogenesis
		1.6.1 Pharmacological Interventions
		1.6.2 Non-pharmacological Interventions
	1.7 Concluding Remarks
	References
2: Application of Nanotechnology in Stroke Recovery
	2.1 Introduction
	2.2 Pathophysiology
	2.3 Current Strategies
	2.4 The Need for Nanotechnology
	2.5 Nanotechnology
	2.6 Nanoparticles Against Stroke
	2.7 Polymeric Nanoparticles
	2.8 Nanocarriers
	2.9 NanoScaffolds
	2.10 Nanomedicine
	2.11 Nanotherapy
	2.12 Safety and Limitations
	2.13 Summary
	References
3: Nanotechnology: A Daydream for Advanced Imaging, Diagnosis, and Therapeutic Approach for Cerebral Ischemia
	3.1 Introduction
	3.2 Pathophysiology of Cerebral Ischemia
	3.3 Conventional Therapeutic Trajectory
		3.3.1 Therapeutic Agents for the Treatment of Cerebral Ischemia
			3.3.1.1 Thrombolytic Drugs
			3.3.1.2 Neuroprotective Drugs
			3.3.1.3 Platelet Aggregation Blockers
		3.3.2 The Limitations Associated with the Conventional Trajectory
	3.4 Nanotechnology - An Unfold Blueprint in Imaging and Treatment of Cerebral Ischemia
		3.4.1 Polymeric Nanoparticles
		3.4.2 Lipid-based Nanoparticles
		3.4.3 Other Types of Nanoparticles
	3.5 Exploitation of Certain Advanced Technology for Imaging and Diagnosis of Cerebral Ischemia
		3.5.1 Imaging/Diagnosis by Magnetic Resonance Imaging Technique
		3.5.2 Imaging/Diagnosis by Computed Tomography
		3.5.3 Imaging/Diagnosis by Positron Emission Tomography
	3.6 Limitations and Prospects
	3.7 Conclusion
	References
4: Cell-Mediated Neurorestorative Mechanisms Underpinning Beneficial Effects in Ischemic Stroke
	4.1 Introduction
	4.2 Stem Cell Types for Stroke Recovery
	4.3 Mechanisms Underlying Neuroprotection in Stroke
	4.4 Cell Replacement
	4.5 Neurogenesis
	4.6 Paracrine Signaling or Bystander Effect
	4.7 Immunomodulation
	4.8 Synaptogenesis
	4.9 Apoptosis
	4.10 Conclusion
	References
5: Induced Pluripotent Stem Cells for the Treatment of Neurodegenerative Disease: Current and Future Prospects
	5.1 Introduction
		5.1.1 Alzheimer´s Disease
		5.1.2 Parkinson´s Disease
		5.1.3 Amyotrophic Lateral Sclerosis (ALS)
		5.1.4 Huntington´s Disease
	5.2 Conclusion
	References
6: Imaging of Stem Cell Therapy for Stroke and Beyond
	6.1 Introduction
	6.2 Real-Time Imaging of Stem Cell Delivery
	6.3 Long-Term Tracking of Cell Survival and Migration
		6.3.1 Preclinical Bioluminescence Imaging
		6.3.2 Preclinical and Clinical Imaging Techniques
		6.3.3 Reporter Genes
		6.3.4 Multimodal Imaging
	6.4 Imaging of Cell Function
	References
7: Nanomedicine-Mediated Stem Cell Therapeutics in Stroke
	7.1 Introduction
	7.2 Current Status of Stroke
	7.3 Therapeutic Strategies
		7.3.1 Drug Therapeutics
		7.3.2 Stem Cell Therapeutics
			7.3.2.1 Treatment Conditions
				Location of Infarct
					Age and Sex Effects
					Comorbidities
				Dosage
				Route of Administration
				Therapeutic Time Window
			7.3.2.2 Mechanism of Action of Stem Cell
				Stem Cell Homing, Tracking, and Survival
				Pathway of Action
	7.4 Summary and Future Prospective
	References
8: The Influence of Preconditioning on the Homing Behavior of Stem Cells
	8.1 Introduction
	8.2 Stem Cell Homing
	8.3 Factors Influencing Stem Cell Homing
	8.4 Timing of Administration of Cells
	8.5 Optimizing the Route of Administration of Cells
	8.6 Preconditioning of Cells for Improved Homing
	8.7 Hypoxia Preconditioning
	8.8 Growth Factors
	8.9 Chemical and Pharmacological Priming
	8.10 Chemokines: SDF1/CXCR4
	8.11 Stem Cell Tracking
	8.12 Conclusion
	References
9: Role of MicroRNAs in Stroke Pathology and Recovery
	9.1 Introduction
	9.2 MiRNA Biogenesis and Function
	9.3 Canonical Pathway
	9.4 Non-canonical Pathway
	9.5 Neurogenesis in Stroke
	9.6 MiRNAs and Stroke
	9.7 MicroRNAs and Blood-Brain Barrier
	9.8 MiRNA in Preconditioning-Induced Neuroprotection in Stroke
	9.9 MiRNA-Based Therapeutics for Stroke
	9.10 MicroRNAs Mediated Neurogenesis in Stroke
	9.11 Conclusions
	9.12 MicroRNA in Neurogenesis Post Stroke
	References
10: Exosomes as a Diagnostic Tool and Stem Cells´ Exosomes as a Promising Cell-Based Cell-Free Therapeutic Tool for Ischemic S...
	10.1 Introduction
	10.2 What Are Exosomes? Their Biogenesis and Functions
	10.3 Exosomes as Biomarkers for Stroke
	10.4 Exosome Therapy for Ischemic Stroke Recovery
		10.4.1 Direct Beneficial Effects on Ischemic Areas
			10.4.1.1 Exosomes for Improved Neurogenesis and Reduced Glia Scaring
			10.4.1.2 Exosomes for Improved Angiogenesis Following Stroke
			10.4.1.3 Exosomes for Repair of Blood-Brain Barrier (BBB)
		10.4.2 Secondary Beneficial Effects of Exosomes
			10.4.2.1 Anti-inflammatory and Immune-Related Outcomes
	10.5 Exosomal Cargo, Importance for Recovery Following Ischemic Stroke
		10.5.1 Exosomes Intrinsic Factors
		10.5.2 Modified/Synthetic Exosomes as Vehicles for Drug Delivery
	10.6 Exosome Source, Is There a Difference Between Cell Sources?
	10.7 Exosomes in Clinical Trials of Ischemic Stroke
	10.8 Limitations of Exosome Therapy for Stroke
	10.9 Conclusions
	References
11: Role of Nanomedicine in Treating Ischemic Stroke
	11.1 Introduction
	11.2 Stem Cells for Regenerative Therapy of Stroke
		11.2.1 Mesenchymal Stem Cells (MSc)
		11.2.2 Neural Stem Cells (NSc)
		11.2.3 Embryonic Stem Cells (ESc)
		11.2.4 Induced Pluripotent Stem Cells (iPSc)
	11.3 Challenges in Stem Cell Therapies for Ischemic Stroke
	11.4 Tracking Stem Cells
	11.5 Role of Nanoparticles in Stroke Therapy
		11.5.1 Nanomedicines Transporting Oxygen to the Ischemic Brain
		11.5.2 Nanomedicines Regulating Excitotoxicity and Ion Imbalance
		11.5.3 Nanomedicines Reducing Oxidative Stress
		11.5.4 Nanomedicine Reducing Apoptosis
		11.5.5 Nanomedicines Regulating Immune Response and Inflammation
		11.5.6 Nanomedicines Inhibiting Pro-inflammatory Mediators
		11.5.7 Nanomedicines Regulating Cells Involved in Inflammation
		11.5.8 Nanomedicines Promoting Tissue Repair Add more literature here in terms of stroke
	11.6 Carbon Nanotubes (CNT)
		11.6.1 Single-Walled Carbon Nanotubes (SWNTs)
		11.6.2 Multi-Walled Carbon Nanotubes (MWCNT)
	11.7 Liposomes
	11.8 Hydrogels
	11.9 Cell-Derived Nanovesicles
		11.9.1 Quantum Dots
		11.9.2 Nanodiamonds
		11.9.3 Iron Oxide Particles
			11.9.3.1 Micron-Sized Superparamagnetic Iron Oxide Particles (MPIOs)
			11.9.3.2 Superparamagnetic Iron Oxide Nanoparticles (SPIONs)
			11.9.3.3 Fluorescent Magnetite Nanocluster (FMNC)
		11.9.4 Black Phosphorus
	11.10 Prospects and Challenges of Nanomedicine-Based Stroke Treatment
	11.11 Summary
	References
12: Insights into Therapeutic Targets in Stroke
	12.1 Introduction
	12.2 Therapeutic Targets in Stroke
		12.2.1 Ischemic Penumbra
			12.2.1.1 Apoptosis
			12.2.1.2 Caspases
			12.2.1.3 Free Radicals
		12.2.2 Ion Channels
			12.2.2.1 Na+ Channels
			12.2.2.2 Ca2+ Channels
		12.2.3 Modifications of Glutamatergic Signaling
		12.2.4 Activated Protein C
		12.2.5 GABA Receptors A
		12.2.6 Antioxidant Levels
		12.2.7 Reperfusion
	12.3 Nanotechnology in Stroke Diagnosis
		12.3.1 Metal Nanoparticles
			12.3.1.1 Microsized Iron Oxide (MPIO) Particles
			12.3.1.2 Superparamagnetic Iron Oxide Nanoparticles (SPIONs)
			12.3.1.3 Perflurocarbon Nanoparticle (PFC)
		12.3.2 Quantum Dots
		12.3.3 Polymeric Nanoparticles
		12.3.4 Dendrimers
	12.4 Nanotechnology in Targeting Stroke Therapy
	12.5 Nanocarriers Used in Stroke Therapy
		12.5.1 Liposomes
		12.5.2 Polymeric Nanoparticles
			12.5.2.1 Chitosan
			12.5.2.2 Dendrimer
		12.5.3 Bioengineered Nanoparticles
			12.5.3.1 ROS-Responsive NPs
			12.5.3.2 Protease-Responsive NPs
		12.5.4 Biomimetic Nanoparticles
			12.5.4.1 Erythrocyte Membrane Nanovesicles
			12.5.4.2 Platelet Membrane-Derived Nanovesicles
			12.5.4.3 Exosomes
			12.5.4.4 Mesenchymal Stromal Cell (MSC)
			12.5.4.5 R3V6 Peptide (with a 3-Arginine Block and a 6-Valine Block)
		12.5.5 Inorganic Nanoparticles
			12.5.5.1 Ceria Nanoparticles (E-A/P-CeO2)
			12.5.5.2 Platinum Nanoparticles (nPt)
			12.5.5.3 Carbon Nanotubes (CNT)
			12.5.5.4 Black Phosphorus
		12.5.6 Hydrogels
		12.5.7 Lipid Nanofomulations
			12.5.7.1 Nanostructured Lipid Carriers (NLCs)
	12.6 Nanoparticles Targeting Receptors in Stroke
		12.6.1 EPO Receptor (EPOR)
		12.6.2 Transferrin Receptor (TfR)
		12.6.3 CXCR4 (C-X-C Chemokine Receptor Type 4)
		12.6.4 Low-Density Lipoprotein (LDL) Receptors
		12.6.5 Lactoferrin Receptors (Fig. 12.7)
	12.7 Nanoparticles Targeting Brain Microvessels
		12.7.1 Integrin αvβ3
	12.8 Limitations and Future Perspectives
	References
13: Signaling Pathways of Interest for Enhancing Recovery from Ischemic Stroke
	13.1 Introduction
	13.2 Mechanisms of Clot Formation
		13.2.1 Platelet Activation and Aggregation
		13.2.2 Coagulation Cascade
		13.2.3 Role of Inflammation in Stroke
	13.3 Enhancement of Neurogenesis
		13.3.1 Role of Neurotransmitters in Neuroregeneration
		13.3.2 Angiogenesis During Neurogenesis
		13.3.3 Lifestyle Interventions for Increasing BDNF
			13.3.3.1 Role of Intermittent Fasting in Neuroplasticity
			13.3.3.2 Role of Exercise in Neuroplasticity
			13.3.3.3 Other Factors Affecting BDNF Level
		13.3.4 Role of Interleukins in Neuroregeneration
	13.4 Conclusion
	References