The Textbook of Nanoneuroscience and Nanoneurosurgery

Mission Statements
	SBMT Mission Statement
	WBMF Mission Statement
	NCNBE Mission Statement
	BTIP Mission Statement
Preface
Editors
Assistant Editors
Contents
1: From Nanotechnology to Nanotechnology/Nanoneurosurgery and Nanobioelectronics: A Historical Review of Milestones
	Introduction
	What Is Nanoneurosurgery and Nanoneuroscience?
	Nanomaterials in Ancient Times
	Early Pioneers in Nanotechnology and Nanomedicine
		Feynman’s Lecture
		Naming of Nanotechnology
		Molecular Nanotechnology
		Nanomedicine
	Technological Advancements Crucial for Nanotechnology Development
		Electron Microscope
		Scanning Tunneling Microscopy and Atomic Force Microscopy
		Colloid/Interface Science and Surface Engineering
		Role of Quantum Physics in the Advancement of Nanotechnology
	Groundbreaking Events in Nanotechnology
		New Carbon Allotropes
		Quantum Dots (QDs)
		Single Electron Tunneling Transistor
		DNA and Gold Colloids to Assemble Inorganic Materials
	Recent Medical and Neuroscientific Advancements Using Nanotechnology
		Early Dawn of Nano-Based Drug Delivery
		Medical Use of Nanomaterials
	Other Important Developments in Nanotechnology
		Nanoparticles
		Dendrimers
		Liposomes
		Nanotechnology for COVID-19: Therapeutics and Vaccine Research
		Abraxane
		Evading the Reticuloendothelial System (RES)
		The Enhanced Permeability and Retention (EPR) Effect
	Nanotechnology and the Nervous System
	Targeted Drug Delivery
		Biomaterials and Regenerative Medicine
	Challenges of Applying Nanotechnology to Nanoneuroscience and Nanoneurosurgery
	Establishment of the National Nanotechnology Initiative
	Role of the US Congress and White House in the Advancement of Nanoneuroscience and Nanoneurosurgery
	Conclusions
	References
2: Nanoneurology and Nanoneurosurgery
	Introduction
	Targeted Delivery of Nanoparticles
	Encapsulation of Nanoparticles
	Administration of Nanoparticles
	Circulation of Nanoparticles
	Target Specificity of Nanoparticles
	Delivery of Nanoparticles to the CNS
	Neurosurgical Applications of Nanotechnology (Nanoneurosurgery)
	Imaging of Brain Tumors
	Contrast Agents for Enhanced Neuroimaging
	Gold Nanoparticles to Detect Early-Stage Alzheimer’s Disease
	Neural Interfaces
	Neuroprotection
	Neuro-Oncology
	CNS and Peripheral Nervous System Tissue Repair
	Nanorobotics for Neurosurgery
	Conclusions
	References
3: Nanopolymers and Nanoconjugates for Central Nervous System Diagnostics and Therapies
	In memory of Lucien M. Levy. Introduction
		The Central Nervous System (CNS), Malignancies, and Current and Developing Therapies
	Nanoparticle Drug Delivery
		What Are Nanoparticles (NPs)?
		The Mechanisms of Action of NPs
		Polymeric Nanoparticle (PNP) Synthesis and Types
		PNP Advantages, Limitations, and Current Research
	Polymeric Nanoconjugates (PNCs)
		An Overview, Mechanisms, and Synthesis
		PNC Advantages, Limitations, and Current Research
		PNC Toxicity
	Summary
	References
4: Micelles, Liposomes, and Extracellular Vesicles: Lipid Nanovesicles for Central Nervous System Drug Delivery
	Introduction
	Historical and Biochemical Bases of Lipid Vesicles
	Nanomicelles, Nanoliposomes, and Extracellular Vesicles
		Nanomicelle and Nanoliposome Structure and Production
		Extracellular Vesicle Biology and Classification
		Selection of the EV Cargo Proteins
		EV Isolation and Characterization
	Nanoparticle Cellular Transport Mechanisms
		Cellular Uptake of Lipid Nanovesicles
		Cellular Uptake of EVs
	Clinical Applications of Lipid Nanovesicles
		Clinical Applications of Nanomicelles and Nanoliposomes
		Clinical Applications of EVs
	Conclusions and Future Considerations
	References
5: Peptide- and Protein-Based Nanoparticles
	Introduction
	Nanoparticles with a Core of Protein or Peptide
		Human Serum Albumin (HSA) Core Nanoparticles
			Human Serum Albumin Core Nanoparticles for Photodynamic Therapy
			HSA Core Nanoparticles for CNS HIV Infection
		Lipoprotein Core Nanoparticles
		Protein Cage Nanoparticles
		Vault Nanoparticles
	Nanoparticles with Protein or Peptide Surface Ligands for Receptor Targeting
		Polymeric Nanoparticles with Surface Peptide Ligands
		Polymeric Nanoparticles with Surface Proteins
		Nanoparticles with Surface Antibodies
			Polymeric Nanoparticles Conjugated to Antibodies
			Liposomes Conjugated to Antibodies
			Iron Oxide Nanoparticles Conjugated to Antibodies
		Iron Oxide Nanoparticles Conjugated to Fluorescent Dyes
		Liposomal Nanoparticles Conjugated to Interleukin-13
		Gold Nanorods Conjugated to Aptamers
			Magnetic Nanoparticles Conjugated to Antibodies and Gold Nanospheres Conjugated to Antibodies and DNA for Highly Sensitive Detection of Amyloid Protein in Cerebrospinal Fluid (CSF)
		Short Cationic Amphiphilic Peptides Conjugated to the TAT Protein and a Cholesterol Core
	Conclusions
	References
6: Endohedral Metallofullerenes, Iron Oxide Agents, and Gold Nanoparticles for Brain Imaging
	Introduction
	Endohedral Metallofullerenes (MFs)
	MRI Relaxivity Properties
	Applications of Metallofullerenes
	Iron Oxide Contrast Agents
		Molecular MRI Using USPIOs
		Microparticles of Iron Oxide
		Molecular MRI Using MPIOs
	Clinical Translation of MPIOs
	Gold Nanoparticles
		Photoacoustic Imaging and Photothermal Therapy Using GNPs
		Multimodal Imaging Using GNPs
		Clinical Applications of GNPs
	Conclusions and Future Perspectives
	References
7: Carbon-Based Nanoplatforms: Types and Applications in Neurological Disorders
	Introduction
	Carbon Nanotubes (CNTs) and Their Synthesis
	Applications of Carbon Nanotubes in Neurological Diseases
	Fullerenes
	Nanodiamonds
	Synthesis of Nanodiamonds
	Biomedical Applications of Nanodiamonds
	Graphene and Graphene Quantum Dots
	Biomedical Applications of Graphene
	Toxicity of Carbon-Based Nanomaterials
	Conclusions
	Bibliography
8: Dendritic and Nanostructured Boron Compounds for Cancer Therapy
	Introduction to Nanomaterials and Dendrimers
	Advantages of Nanomaterials and Dendrimers
	Biodistribution Studies on Various Cancer Cell Lines
	Nanomaterials and Dendrimers for Treatment of Different Types of Brain Cancers
	BNCT for Treatment of Brain Cancer
	Conclusions
	References
9: Ligand-Based Targeting of Therapeutic and Imaging Agents for Cancer
	Introduction
	Ligand-Based Conjugates for Tumor Imaging and Therapy
		Peptide-Based Conjugates
		The RGD (Arg-Gly-Asp) Peptide for Integrin Targeting
		Somatostatins
		Bombesin (BBN)
		Cholecystokinin (CCK)/Gastrin Peptide
		Vasoactive Intestinal Peptide (VIP)
		α-Melanocyte-Stimulating Hormone (α-MSH)
		Neurotensin (NT)
		T140
		Exendin-4
		Neuropeptide Y (NPY)
		Substance P
		Tumor Molecular Targeted Peptide 1 (TMTP1)
		Macromolecule-Based Conjugates
		Epidermal Growth Factor Receptor (EGFR)
		Vascular Endothelial Growth Factor (VEGF)
		Membrane Transferrin Receptor (TfR)
	Ligand-Based Nanotherapeutics for Brain Tumors
		Polymeric and Liposomal Nanoparticles
		Carbon Nanomaterials
		Dendrimers
		Gold Nanoparticles (AuNPs)
		Iron Oxide Nanoparticles
	Conclusions
	References
10: Nano-Assisted Immune-Based Targeting in Cancer
	Introduction
		Immune-Based Targeting Against Cancer
	Conclusions
	References
11: Directed Drug Convection Using Magnetic Nanoparticles as Therapeutic Carriers Meeting the Challenge of Specific Brain Pharmacotherapeutics, Non-ligand-Based Central Nervous System Targeting, Including Magnetic Focusing
	Introduction
	Magnetic Nanoparticle’s Introduction
		Drug Delivery
		Targeted Therapy
		Hyperthermia
		Imaging and Diagnostics
		Controlled Drug Release
		Crossing Biological Barriers
		Combination Therapy
		Monitoring Treatment Response
		Regenerative Medicine
		Nanotheranostics
		Noninvasive Treatment
		Multimodal Imaging
		Photothermal Therapy
		Magnetic-Assisted Tissue Engineering
		Veterinary Medicine
		Biocompatibility and Safety
		Brain Drug Delivery Using Magnetic Nanoparticles
		Challenges
	Nanoparticles for the CNS
		Targeted Drug Delivery
		Theranostics
	Convection-Enhanced Delivery
	Superparamagnetic Nanoparticles
	Magnetic Resonance Navigation (MRN)
	Preparation
	Nanotechnology Toward CNS Drug Delivery
		Surface Modifications
	Liposomes
		Small Unilamellar Liposomes (SUVs)
		Multilamellar Liposomes (MLVs)
		Giant Unilamellar Vesicles (GUVs)
			Doxil (Doxorubicin Liposomal)
			AmBisome (Amphotericin B Liposomal)
			Liposomal Nanoparticles for Gene Delivery
			Liposomal Gadolinium-Based Contrast Agents
			ONPATTRO (Patisiran Liposomal)
			DepoDur (Extended-Release Morphine Liposomal)
			Liposomal Encapsulated Cytarabine and Methotrexate
			Liposomes for Parkinson’s Disease
			Liposomal Curcumin
			Liposomes for Alzheimer’s Disease
			Liposomal Nanocarriers for RNA Therapeutics
			Nanoparticles-in-Liposomes (NILs) for CNS Drug Delivery
			Anti-inflammatory Liposomes
	Polymeric Nanoparticles
	Magnetically Directed Drug Convection
	In Conclusion
	References
12: Intralesional and Intraparenchymal Convection-Enhanced Delivery of Nanoparticles
	Introduction
	Physical Principle
	Animal Studies
	Clinical Trials
	Conclusion
	References
13: Transport of Nanoparticles Across Blood–Brain Barrier
	Introduction to Blood–Brain Barrier
	Structure of BBB
	Functions of BBB and Methods of Crossing
	Alterations of BBB
	Nanoparticle Methods of Crossing BBB
	Nanoparticle Archetypes
	Potential Barriers to Nanoparticle Application
	Conclusions
	References
14: Nanomedicine Treatment Strategies That Exploit Unique Characteristics of Tumor Vasculature and Microenvironment
	Introduction
	Aberrant Tumor Vascular Architecture
	Altered Oxygenation Level, Metabolism, and Homeostasis in Tumor Microenvironment
	Irregular Proteolytic Activities in Tumor Microenvironment
	Heterogeneous Blood Flow in Tumor Tissue and Circadian Fluctuation Mechanism for Tumor Growth
	Enhanced Permeability and Retention Effect for Macromolecular and Lipidic Agents
	Canine Cancer Models for Nanomedicine Preclinical Testing
	Conclusion
	References
15: Focused Ultrasound for Non-invasive Neuromodulation
	In memory of Warren S. Grundfest Introduction
		Critical Barriers to Progress in the Field of Treatments for CNS Disorders
		Development of Ultrasound
		Therapeutic Ultrasound
		Ultrasound Parameters and Bioeffects
		Biomedical Engineering Challenges to Transcranial Ultrasound
	Neural Applications of Focused Ultrasound
		Focused Ultrasound Ablation
		Ultrasound-Mediated Bioeffects
		Ultrasound Facilitation of Drug Transfer through BBB
		Sonoporation
		Ultrasonic Neuromodulation
		Ultrasonic Neuromodulation in the Periphery
		Ultrasound-Induced CNS Neuromodulation
	Conclusion
	References
16: Nanostructured Surfaces for Intracerebral Neurotransmitter Recording
	Introduction
	Microelectrode Arrays for Intracerebral Neurotransmitter Measurements
	Nanostructure of Microelectrode Array Recording Sites
	Conclusions
	References
17: Therapy for Neuropathic Lysosomal Storage Diseases
	The Current Standard of Care and Research for LSDs
		Enzyme Replacement Therapy
			Gaucher Disease
			Fabry Disease
			Pompe Disease
			MPS
		Research into the Effective Use of ERT
		Next Generation Enzyme Replacement Therapy
	Stem Cell Transplantation
	Gene Therapy
		Substrate Reduction
		Chaperones
		Reducing Degradation of the Deficient Enzyme
		Lysosome Exocytosis
		Proteostasis Regulators
	Using Nanotechnology to Develop Novel Therapeutics for LSDs
		Structural Modifications of Nanoparticles
		Modification of Nanoparticles for CNS Targeting Enzymes
		Intercellular Adhesion Molecule 1 (ICAM-1)-Mediated Targeting and Endocytosis
	Conclusions
	References
18: Nanotechnology for Cerebral Aneurysm Treatment
	Introduction
	Modern Solutions for Diagnosis and Treatment
		Nanostructure Platforms
		Embolization Materials
		3D Printed Bioelectronics
		Role of Nanoparticles
	Future Outlook
	References
19: Applications and Recent Advances of Nanotechnology and Nanomedicine in the Diagnosis and Therapy of Stroke
	Dr. Mehrnaz Gholami is the lead author for this chapter. Introduction
	Therapeutic Effects of Nanoparticles and Nanotechnology in Stroke
	Blood-Brain Barrier
	Applications of Nanotechnology in the Central Nervous System in Stroke Therapy
	Neuron Preservation by Applications of Nanomedicine on NMDA and AMPA Receptors
	Therapeutic Intervention to Treat Stroke
	Magnetic-Guided Targeting
	Vascular Endothelium in Cases of Stroke
	Nanoparticles and Oxidative Stress in Stroke
	Enhancing Gene Delivery by Nanomaterials in Stroke
	Application of Nanomaterials for Brain Drug Delivery
	Nanomedicine and Tissue Engineering in Brain Damage Caused by Stroke
	Neuroimaging Techniques to Diagnose Patients with Stroke
	Immunoliposomes for Diagnosis of Rupture-Prone Vascular Anomalies of Central Nervous System
	Nanotheranostics for the Brain
	Nanotechnology and Nanomedicine in Stroke Therapy: Advances and Recent Findings
	Clinical Trials on the Application of Nanotechnology in Stroke
	Conclusion
	References
20: Molecular Medical Devices for Nanoneurosurgery
	Introduction
		The Potential of Molecular Medicine
		Understanding Molecular Machines
		Harnessing Molecular Mechanisms for Nanoneurosurgery
		Innovations in Molecular Imaging
		Challenges and Ethical Considerations
	The Phrases “Self-assembly” and “Self-organization”
	Origins of Neurosurgery and Cellular Assembly in Neural Development
		Tissue Organization and Neurulation
		Cellular Movement and ECM Interactions
		Reimagining Cellular Regeneration
		Central Nervous System and Nanoneurosurgery
		Purpose and Impact of Nanoneurosurgery
		Recent Developments
		Four Ps of CNS Regeneration: A Framework for CNS Regeneration
		Preserve
		Permit
		Promote
		Plasticity
		Conclusions
	Nanotechnology in Medicine: A Decade of Progress
		Nanomedicine Evolution
		New Developments
		Diagnostic Advancements
		Nanoscaffolds: Building and Rebuilding at the Nanoscale
		Nanomedicine: Current Paradigm and Promise
		Latest Insights
		A Deeper Dive into Nanomedicine
			Distinction, Development, and Promise
		Developments Over the Decade
			Personalized Nanomedicine
			Enhanced Drug Delivery
	Nanomaterials
		Advancements in Nanomaterials and Self-assembly in Medicine
			Understanding Nanomaterials
		The Beauty and the Evolving Dynamics of Self-assembly
		In Retrospect and Forward Thinking
		Advancements in Self-assembling Peptides and Multidimensional Biomaterials
			Journey with (RADA)4 and Beyond
			Unveiling the EAKA Sequence
		Self-assembly and the Power of Environment
		Beyond Two Sequences: The Universe of Combinatorial Possibilities
		In Retrospect and a Glimpse into the Future
		Advances in SAPs
		Some Other Noteworthy SAPs Include
			(RADA)4
			EAKA
			RAD16-I (Ac-(RADA)4-CONH2)
			RAD16-II
			KLDL, KLDF, and DLEU
			Protein Amyloids
			FKFE
			FEFEFKFK (P11–4)
			MAX1 (VKVKVKVKVDPPTKVKVKVKV-NH2) and MAX8
			Q11 (QQKFQFQFEQQ)
		Biomimetic Peptides
		Peptide Amphiphiles (PAs)
		Recent Advancements
	Nanomedicine: A Revolution at the Nanoscale
	Nanoneurosurgery: Precision at the Nanoscale
	CNS Regeneration: Bridging the Neural Gap
	Surgical Method of the Optic Nerve
	Results
		Modern Advances
	CNS Regeneration After Acute Injury
		Nano Neuro Knitting
			CNS Regeneration After Acute Injury: The Promise of Nano Neuro Knitting
				Introduction
				Concept of Nano Neuro Knitting
				Methodology
				Benefits and Implications
					The Implications of Nano Neuro Knitting Are Profound
				Future Prospects
	Surgical Methods for Eye Vision Restoration: Exploring Nano Neuro Knitting
	Other Agents to Enhance Regeneration Results
	Recent Advances
	CNS Regeneration After Chronic Injury
	Surgical, Imaging, and Behavioral Protocol
	Surgical, Imaging, and Behavioral Protocols: A Comprehensive Guide
		Baseline Imaging
		Transection of BSC and (RADA)4 Treatment
		Animal Behavioral Assessment
		Treatment Surgery
		Intravitreal MnCl2 Injections
		Horseradish Peroxidase OT Tracing
		Three-Dimensional MRI
		Results
		Posttreatment MRI
		Axonal Regrowth
		Chronic CNS Injury Visualization (as per Fig. 20.11)
		Regenerating the Spinal Cord
		In Vitro Preparations
			Pretreatment of (RADA)4
		SchCs and NPCs in 3D Culture Within (RADA)4
		Surgical Procedures
		Results
		Stroke
	Summary of the Experiment on (RADA)4’s Therapeutic Potential in Rats with RVHT and ICH
	Surgical Method in Detail
		Results
	Objective Measures in CNS Evaluation
	3D Environments in Stem Cell Preservation and Regeneration
	Methods: Stem Cell Cultures, Transplantation, and In Vivo Applications
		Conclusion
	In Vitro Results
		Primary Neurons
		Conclusion
		Neural Precursor Cells Growth in Different (RADA)4 Concentrations
		Overall Observations on Branching
	Interpretation and Future Outlook
	In Vivo Evaluation of (RADA)4 for Neural Repair
		Concluding Remarks
	Advanced Surgical Techniques Using (RADA)4 for Neural Repairs
	Nanotechnology and Safety
	Final Reflections: The Promise of Nanotechnology in Medicine
	References
21: Applications of Nanotechnology in Epilepsy
	Introduction
	Evaluation for Epilepsy Surgery: Nanoneurosurgery Advancements
		Magnetoencephalography to Localize Seizure Onset
		Covalently Conjugated Magnetonanoparticles
		Localizing Electroencephalographic Abnormalities Using Neuroimaging
		Diffusion Tensor Imaging and Tractography
		Optical Imaging
	Closed-Loop Seizure Prevention Nanosystems
		Microelectrode Recordings in Seizure Localization, Detection, and Prediction
		Closed-Loop Seizure Detection
		Hybrid Neuroprosthetics
	Drug Delivery Nanotechnology
		Direct Brain Delivery Systems
			Intracerebroventricular Administration
			Intracerebral Administration
			Convection-Enhanced Delivery
			Blood–Brain Barrier Modification
			Drug Modification
	Recent Findings
	Conclusions
	References
22: Applications of Nanotechnology to Diseases of the Spine
	Introduction
	Diseases of Application
		Degenerative Disease of the Spine
		Tumor, Trauma, and Infections
		Augmentation for Compression Fractures of the Vertebral Body
	Current Applications of Nanotechnology in Spinal Surgery
		Spinal Fusion
		Nanotexturing of Structural Implants for Spinal Fusion
		Bony Fusion/Arthrodesis
		Calcium Phosphate Cement (CPC) as Bone Scaffold
		Poly(lactic-co-glycolide) as Bone Scaffold
		Vertebroplasty and Kyphoplasty for Vertebral Compression Fractures
		Disc Substitutes
		Cervical Artificial Disc Replacement
		Lumbar Artificial Disc Replacement
		Three-Dimensional Printing
	Future Applications for Nanotechnology in Spinal Surgery
	References
23: Nanoparticle-Based Treatment and Imaging of Brain Tumors Potentials and Limitations
	Introduction
	Brain Tumor
		Overview
		Current Treatments
		Limitations of Conventional Drug Treatment
			Multidrug Resistance
			Blood–Brain Barrier
			Blood–Tumor Barrier
			Blood–Cerebrospinal Fluid Barrier
		Traditional Methods for Overcoming the BBB
			Transcranial Delivery Methods
			Chemical and Biochemical Methods
		Enhanced Permeability and Retention Effect
	Nanoparticles for Treating and Imaging Brain Tumors
		Nanoparticle-Based Anticancer Treatments
			Liposomes
			Solid Lipid Nanoparticles
			Polymers
			Polymer Micelles
			Dendrimers
			Exosomes
			Nanoghosts
			Cancer Cell Membrane-Coated Nanoparticles (CCMCNPs)
		Other Nanoparticles for Killing Cancer Cells
			Nanoparticle Photodynamic Therapy
			Photothermal Ablation
			Nucleotide Delivery
			Ferroptosis Therapy
		Nanoparticles for Brain Tumor Imaging
			Superparamagnetic Iron Oxide
			Intraoperative MRI
			Magnetic Particle Imaging (MPI)
			Nanoparticles for Treatment and Imaging
		Future of Nanoparticles
			Regulatory Considerations
			Future Research Objectives
	Conclusions
	References
24: Tumor-Targeted Nanodrugs for the Treatment of Primary Brain Tumors
	Introduction
	Nanoparticle Design
	Preclinical Applications
		Doxorubicin
		Paclitaxel
		Topoisomerase I Inhibitors
		Methotrexate
		Magnetic and Metallic Nanoparticles
		Nonsteroidal Anti-inflammatory Drugs
		Targeted Boron Compound Delivery for BNCT
		Polycefin
		Nucleotides
		Ferroptosis
	Emerging Clinical Applications
	Challenges
	Conclusion
	References
25: Application of Nanotechnology in the Diagnosis and Treatment of Brain Metastases
	Introduction
	Nanoparticle Targeting of Brain Metastases
	Nanoparticle Types and Therapeutic Properties
	Drug Delivery via Nanoparticles
	Thermic and Photonic Nanoparticle Therapies
	Theranostic Applications
	Nanoparticle-Enhanced Immunotherapy
	Conclusion
	References
26: Nanotechnology in Brain Tumors: Neurosurgical Perspectives
	Introduction
	Nano-pathophysiology
		Blood–Brain Barrier or Neurovascular Unit
		Glymphatic Pathway: A New Discovery by Nanotechnology
	Applications of Nanotechnology to Imaging of Brain Tumors
		Iron Oxide Nanoparticles
		Quantum Dots
		Gold Nanoparticles
		MRI-Photoacoustic-Raman Nanoparticle-Based Brain Tumor Imaging
	Pharmacologic Interventions
		Polymer Nanoparticles
		Liposomes
		Dendrimers
		Micelles
		Focused Ultrasound Disruption of BBB
	Basic Principles of Brain Tumor Surgery
	Brain Tumor Nanosurgery: State of the Art and Future Directions
	Conclusions
	References
27: Using Nanoparticles in Diagnosis and Treatment of CNS Infection
	Introduction
	Pathogenesis
		Epidemiology and Patient Groups
		Diagnosis and Imaging
		BBB and CSF
	Nanomedicine in CNS Infections
		Nanotechnology in the Detection of CNS Infections
		Additional Nanotechnology in the Detection of CNS Infections
		Nanoparticles in Delivering Treatment for CNS Infections
		Additional Nanoparticle Technology in Delivering Treatment for CNS Infections
	Conclusion
	References
28: Nanotechnology in the Prevention and Treatment of Neurological Disorders
	Introduction
	Nanotechnology: Focus on the Molecular and Cellular Mechanism of Movement Disorders
	Applications of Nanotechnology in Drug Delivery to the Central Nervous Against Movement Disorders
		Material Properties of Nanoparticles
		Influential Factors That Facilitate Successful Drug Delivery Across BBB
	Nanotechnology Based on the Use of Carbon Nanoparticles and Carbon Systems
		Fullerene Derivatives
		Carbon Nanotubes
	Nanotechnology for Gene Therapy
		Nonviral Nanotechnology Vectors as Vehicles
		Viral Nanotechnology Vectors as Vehicles
		Nanoparticle-Based Gene Therapy
	Nanotechnology for Cell Therapy
	Conclusion
	References
29: Nanomedicine in Demyelinating Disease Application to Diagnosis and Therapy in Multiple Sclerosis
	Introduction
		Definition and Classification of MS
		Etiology and Pathogenesis
		Challenges in MS Treatment
	Encapsulation of MS Therapeutics
		Liposomes
		Solid Lipid Nanoparticles
		Aquasomes
		Denrimers
	Oligonucleotide Delivery
		DNA Vaccines
		Inverse Vaccines
		Antisense Oligonucleotides
		Neuroprotection to Complement MS Drug Therapy
	Magnetic NPs
		Iron Oxide Nanoparticles
		Functionalized Nanoparticles
		Quantum Dots
		Mesenchymal Stem Cell Labeling
		Placenta-Derived Pluripotent Adherent Cells (PDA Cells)
	Conclusion
	References
30: Applications of Nanotechnology in Degenerative Disorders of the Brain
	Introduction
	Nanodiagnostics
	Nanoimaging
	Nanotherapeutics
		Dendrimers
		Gene Therapy
		Stem Cell Therapy
		Drug Delivery and Therapy
		Miscellaneous Examples
	Nanoneuroprotection
		Fullerenes
		Other Neuroprotective Agents
		Drug Therapy for Neuroprotection
	Nanomanipulation
	Nanoneuromodulation
		Carbon Nanofibers
		Carbon Nanotubes
		Nanowires
	Conclusion
	References
31: Brain–Machine Interface and Rehabilitation
	Background
	Component of BMI
	Nanotechnology (Device and Tools for Amplification)
	BMI Technologies
		EEG-Based Technologies
		ECoG-Based Technologies
		Intracortical-Based Technologies
	Neuroprosthesis
	Rehabilitation
	Challenges and the Opportunity of BCI in Rehabilitation
	References
32: Nanobioelectronics for Noninvasive Neural Therapy
	Introduction
		Electromagnetic Fields
		What Causes the Magnetic Field to Form?
		Cellular Electrical Properties
		Electrotherapy for Neural Tissues
	Nanoelectronics for Nerve Regeneration
		Revolutionizing Peripheral Nerve Repair: The Role of Nanotechnology and Advanced Techniques in Addressing Nerve Injuries: Current Treatments
		Unveiling the Synergy of Nanomaterials and Nano-Electronics for Nerve Regeneration
			Carbon Nanomaterials
			Graphene
			Carbon Nanofibers
			Magnetic Nanoparticles
		Nanoelectronics for Neurodegenerative Diseases
		Parkinson’s Disease
			Updates on Deep Brian Stimulation
		Alzheimer’s Disease
			Nanoparticles-Based Electrochemical Sensors and Alzheimer’s Disease
	Nanoelectronics for Cancer Therapy
		Unveiling the Power of Electrotherapy in the Fight Against Cancer: How It Works and Why It Matters
	Electrical Neural Interfacing
		Neural Recording Using Nanoprotrusion Electrodes
		Nanogapbiosensors
	Conclusion
	References
33: In Vitro and In Vivo Techniques to Assess Neurotoxicity of Nanoparticles
	Introduction
	In Vitro Techniques
		Basal Cytotoxicity Screening
	Role of Omics Techniques in the NPs Toxicity Assessment
		Specific Cytotoxicity Screening
	In Vivo Techniques
		Histopathology
		Imaging Techniques
			Positron Emission Tomography
			MRI and MRS
		Analytical Techniques
			Microdialysis
			Open Flow Microperfusion (OFM)
		Behavioral Tests
	Conclusions
	References
34: Nanorobotics for Neurosurgery
	Introduction
	Tools for Nanoscale Surgical Operations
		Femtosecond Laser Systems
		Nanoneedles
		Nanotweezers
		Manufacturing for Tissue Repair in Central and Peripheral Nervous Systems
	Nanoscale Robotic Devices for Automated Surgical Procedures
		Engineered Biological Organisms
		Engineered Biomolecules
		Hybrid Organic/Inorganic Nanorobots
	Inorganic Nanorobotic Components
	Powering Nanorobotic Devices
	Biomimetic Nanorobotic Devices
	Future Considerations for Nanorobotic Neurosurgical Applications
	Conclusion
	References
35: Micro- and Nanotechnologies in Nerve Repair
	Introduction
		Advances in Neural Regeneration Over the Past Decade
			Molecular and Cellular Mechanisms
			Neural Stem Cells (NSCs)
			Extrinsic and Intrinsic Factors
			Biomaterials and Scaffolds
			Neurotrophic Factors
			Gene Therapy
			Optogenetics
			Electrical Stimulation
			Epigenetics
			Combination Therapies
	Peripheral Nervous System (PNS)
	Axonal Repair
		Historical Perspective
		Modern Challenges and Approaches
		Experimental Breakthroughs
		The Assumption of Stem Cells
		Micro- and Nano-Scale Revolution
	Biomaterials in Axonal Repair
		Collagen Tubes
			Mechanism
			Advancement
			Challenges
		Electrospun Nanofibers
			Mechanism
			Advancement
			Challenges
	Nanomaterials for Tubular Conduit Functionalization
		The Integration of Nanotechnology and Tissue Engineering
		Carbon Nanomaterials in Biomedical Applications
	Carbon Nanotubes (CNTs) for Neural Scaffolds
		Categorization and Production of CNTs
		Exceptional Properties of CNTs and Functionalization Strategies
		Biomimetic Qualities of CNTs for Neural Repair
		Carbon Nanotubes (CNTs) in Peripheral Nerve Repair
		Profound Effects of CNTs in PNR
		Concerns and Toxicity
	Graphene in Peripheral Nerve Repair
		Applications of Graphene in PNR
		Electrical Stimulation and Differentiation
		Enhanced Scaffold Strength and Electrical Conductivity
		Nerve Regeneration and Neurite Proliferation
		Graphene in Tubular Conduits
	Carbon Nanofibers (CNFs) in Peripheral Nerve Repair
	Nanodiamonds (NDs) in Peripheral Nerve Repair
		Applications of Nanodiamonds in Peripheral Nerve Repair
	Nanoparticles in Peripheral Nerve Repair
	Magnetic NPs in PNR
		Labelling and Tracing of Neural Cells
		Enhanced Scaffold Properties
		Targeted Drug Delivery
	Nanotechnology for Promoting Neuronal Growth and Myelination
		Neuronal Growth
		Myelination
	Nanotechnology in Combination with Stem Cells
		Schwann Cells (SCs)
		Mesenchymal Stem Cells (MSCs)
		Induced Pluripotent Stem Cells (iPSCs)
		Neural Stem Cells (NSCs)
	Nanotechnology-Enhanced Diagnostics and Monitoring
		Nanoparticle-Based Imaging
		Implantable Nano-Sensors
	Conclusion and Future Perspectives
		Personalized and Precision Medicine
		Regulatory and Safety Considerations
		Integration of Multiple Strategies
		Clinical Translation
		Cost and Accessibility
		Long-Term Outcomes
	Stem Cells in Axonal Repair
		Neural Stem Cells
			Mechanism
			Advancement
			Challenges
		Mesenchymal Stem Cells (MSCs)
			Mechanism
			Advancement
			Challenges
	Nano-Technological Approaches
		Magnetic Nanoparticles
			Advancement
			Challenges
		Nanofiber Channels
			Mechanism
			Advancement
			Challenges
		Protein-Based Approaches
	Axonal Trimming
		Technologies and Methods Used
			Nano-Knife
			Description
			Applications
			Pros
			Cons
		Laser Microbeam Technique
			Description
			Applications
			Pros: Non-contact Method
			Cons
		Chemical Trimming
			Pros
			Cons
		Challenges in Axonal Trimming
			Precision
			Viability
			Collateral Damage
			Scalability
		Future Directions
	Nano-Knife Technique in Axonal Repair
		Introduction
		Design and Structure
			Physical Attributes
			Cutting Precision
		Applications
			In Vitro Use
			In Vivo Use
		Benefits
			Precision
			Physical Robustness
			Versatility
		Challenges and Future Developments
		Conclusion
	Laser Microbeam Technique in Axonal Repair
		Introduction
		Mechanism and Design
			Principle of Operation
			Pulse Duration
		Applications
			Axonal Trimming
			Cellular Studies
		Enhancements and Complementary Techniques
			Photosensitization
		Benefits
			Non-contact Technique
			Precision
			Controlled Energy Delivery
		Challenges and Limitations
			Depth Limitations
			Thermal Concerns
		Future Outlook
		Conclusion
	Physics and Characteristics of Laser Microbeam Technique in Axonal Repair
		Introduction
		Type of Laser
		Wavelength
		Temperature Control
		Pulse Duration
		Advantages of Using Pulsed Lasers
			Minimized Heat Production
			Precision
			Control
			Conclusion
	Chemical Trimming in Axonal Repair
		Enzymatic Degradation
			Proteolytic Enzymes
			Tubulin-Targeting Agents
		Excitotoxic Amino Acids
		Reactive Oxygen Species (ROS) Generation
		pH Modulation
		Targeted Neurotoxins
		Challenges and Considerations
	Axonal Alignment
		Axonal Alignment: Mechanisms and Techniques
		Microelectromechanical Systems (MEMS)
			Introduction
			Role in Axonal Alignment
			Direct Repair Model
		Dielectrophoresis (DEP)
			Principles
			Application in Axonal Alignment
			Cellular Configuration and Contact
			Safety and Cell Viability
			Limitations
			Conclusion
	Axonal Fusion
		Introduction
		Micro-Electrofusion
			Concept and Mechanism
			Experimental Evidence
			Potential Advantages
			Challenges
		Chemical Fusion
			Concept and Mechanism
			Advantages and Limitations
			Challenges and Concerns
		Laser-Induced Membrane Fusion
			Concept and Mechanism
			Experimental Evidence
			Potential Advantages
			Challenges
			Biological Mechanisms
		Mechanical Tension-Based Fusion
			Concept and Mechanism
			Potential Advantages
			Challenges
		Innovations from Vascular Neurosurgery
			Microvascular Techniques
			Robotic Integration
			Conclusion
	Axonal Repair Microdevice
		Axonal Repair Microdevice: An Introduction
			Operative Field Scale
		Three-Step Paradigm for Axonal Repair
			Trimming
			Aligning
			Fusing
		Prototypes and Progress
		Neuronal Survival During Repair
		Implications and Future Directions
			Operative Suite Evolution
			Training and Skill Acquisition
			Potential Applications
			Challenges
			Conclusion
	Conclusion
		The Axonal Challenge
		Stem Cell Research
			Peripheral Nerves as Model Systems
			Technological Advancements
			Reconnection Over Regeneration
			Benchmark for Success
		The Road Ahead
	References
36: Nanotechnology Applications to Pediatric Neurosurgery
	Introduction
	Applications in Hydrocephalus
		Smart Catheters: Reduction of Bacterial Colonization on Ventricular Catheters
		Improving Catheter Design
		Pressure Monitoring Devices
		Flow Rate Monitoring Devices
	Applications in Cerebral Trauma
		Monitoring Devices for Oxygenation and Metabolism
	Applications in Cerebral Arteriovenous Malformation
		Endothelial Targets
		Quantum Dots and Imaging
	Cerebral Ischemia and Magnetic Nanoparticles
	Applications in Tethered Cord Syndrome
		Biomaterials with Decreased Immunogenicity
		Improved Bioactivity in Nanoparticle-Coated Implants with Greater Roughness
	Targeting Cancer: Pediatric Applications
		Chlorotoxin-Labeled Nanoparticles and Gene Therapy
		Magnetic Fluid Hyperthermia
		Plasmonic Nanobubbles as Surgical Tools
		Arsenicals and Hedgehog-Related Tumors
	Future Directions
	References
37: Application of Nanotechnology for Cerebrovascular and Skull Base Disorders
	Introduction
	Nanotechnology a Way of Crossing the BBB
	Nanotechnology for Ischemic Stroke Diagnosis
	Nanotechnology for Ischemic Stroke Management
	Nanotechnology in Diagnosing Adult Primary Brain Tumors
	References
38: Application of Nanotechnology in Acquired Brain Injuries
	Introduction
	Nanoparticles and ABIs Caused by Trauma
	Strategies for Nanoparticle Delivery to the Brain
	Improvement of NPs Availability: From Passive Delivery to Active Delivery System
	Characteristics of NPs
		Composition
			Polymeric NPs
			Lipid-Based NPs
			Inorganic NPs
			Hybrid NPs
	Surface Modification
	Size
	Charge
	Shape
	Nanoscaffolds in ABIs
	Preparation Methods for Nano-Scaffolds
	Nano-Scaffolds in Acquired Brain Injury
	Conclusion
	References
39: microRNAs Mediate Signaling Pathways in Alzheimer’s Disease: Biomarkers and Therapeutic Targets
	Introduction: History of microRNAs and Their Importance in Alzheimer’s Disease (AD)
	Biogenesis Pathways of miRNAs: Canonical and Non-canonical miRNAs
	Regulation of miRNAs Biogenesis
	miRNAs Mediate Signaling Pathways in Neurogenesis, Synaptogenesis, and Synaptic Pruning
	miRNAs Have a Critical Role in Synaptic Plasticity
	miRNAs Mediate Signaling Pathways in Memory Formation/Impairment
	Cross-Talk Between miRNAs and Cholinergic System in AD
	Regulation of Amyloid-β-Precursor Protein by miRNAs
	miRNAs Are Key Regulators in the Process of Aβ Production and Clearance
	miRNAs Regulate the Expression and Phosphorylation of Tau
	Mitochondrial miRNAs in AD
	Interplay Between miRNAs and Oxidative Stress in AD
	miRNAs Delivery via Nanoparticles
	Technologies for miRNA Detection
	Detection of miRNAs with a Nanopore Single Counter
	miRNA Nanotherpeutics and Biomarkers: Potential and Challenges in AD
	Conclusion
	References
40: Retinal Neuromodulation as an Influence on Brain Function by Applying Nanoneuroscience Discoveries
	Introduction
	Neuroanatomy of Visual Signaling
		Cortical Optic Nerve Connections
			Retino-Geniculostriate Pathway (Where Is It?)
			Retino-Geniculostriate Pathway (What Is It?)
		Subcortical Optic Nerve Connections
			Retino-Hypothalamic Pathway (How Am I?)
			Retino-Amygdala Pathway (Am I Safe?)
			Retino-Raphe Pathway (Do I Care?)
			Retino-Pretectal Pathway (How Is My Environment?)
			Retino-Tectal Pathway (Where Is My Body?)
				Superficial vs. Deep Layers of the Superior Colliculus
				Input Projections to the Superior Colliculus
			Accessory Optic System (Where Is My Head/Eye?)
		Blindsight—Geniculo-Extrastriate Pathway (Where/When Is It?)
	Neurophysiology of Visual Processing
		Processing: Before the Optic Nerve
			Pigment Epithelium and Photoreceptors
				Ocular Glymphatic System and Visual Cycles
			Outer and Inner Plexiform Layers
			Ganglion Cells (Including ipRGC) and Axons
		Processing: Beyond the Optic Nerve
			Low-Level Visual Processing (Who Am I?/Am I Safe?/Do I Care?)
			Mid-Level Visual Processing (Where/When Is It?)
			High-Level Visual Processing (What Is It?/What Do I Do About It?)
	Current Visual Diagnostic Testing
		Eyesight Assessment
		Eye Health Assessment
			Vascular Health
				Ocular Perfusion Pressure (OPP)
				Regulation of Retinal Blood Flow: Autoregulation
				Imaging and Quantification of Ocular Hemodynamics
			Neurological Health
		Eye Movement Assessment
			Non-conscious (bottom-up eye movements)
			Conscious (top down eye movements)
	Breakthrough Technologies in Eyecare
		Nanoparticles
		Optogenetics
		Visual Prosthetics
		Artificial Intelligence
		The Future of Eyecare
	Conclusion
	References
41: Bridging the Gap: Nanotechnology’s Impact on Neuroscience—A Systematic Review of Clinical Trial
	Introduction
	Methods
		Study Selection
		Data Extraction
		Quality Assessment
	Results
		Systematic Literature Search and Study Selection
			Years and Geographic Distribution
			Type of Disease
			Clinical Trial Phase
			Type of Nanodrugs
			National vs. Private Grant
	Discussion
	References
42: Nanostructured Boron and Gadolinium Compounds for Neutron Capture Therapy (NCT)
	Introduction
		Introduction to Neutron Capture Therapy
		Mechanism of BNCT
		Early Breakthroughs of Boron Compounds in the Field of BNCT
		Gadolinium: An Underdeveloped Neutron Capture Agent
	Boron-Based Nanomaterials and Their Application in BNCT
		Boron Nitride Nanotubes and Nanoparticles
		Boron Nanoparticles Entrapped Liposome
		Boron Carbide Nanoparticles
		Boron-Based Polymers
		Nanohybrid Consisting of Boron Clusters with Magnetic Core
		Gold Nanoclusters with Boron Carriers
	Gadolinium (Gd)-Based Nanomaterials and Their Applications in NCT
		Liposomes Entrapped Gadolinium-DTPA
		Calcium Phosphate-Based Nanoparticles
		Gd@C82 Metallofullerenes
		Gadolinium-Loaded Chitosan Nanoparticles
	Conclusion and Future Perspective
	References
43: Applications of 3D Bioprinting in Nanoneuroscience
	Introduction
	3D Printing and Nanoneuroscience Applications
		Tissue Engineering and 3D Printing
		3D Printing and Nanomaterials
		Nano Drug Delivery Systems
		Tissue Study
		Neural Tissue Regeneration
		Tissue Regeneration in Peripherical Nervous System
		Tissue Modeling: Neural Tissues and Cancer
	3D Printing in Neurosciences: Applications at the Macro-scale
		Neural Science Education
		3D Printing and Surgical Neurology
		Retraction and Suturing Techniques
		Skull Deformities and Craniosynostosis Repair
		Intraventricular Procedures
		Skull Base Surgeries and Tumor Resection
		Stereotactic Radiosurgery
		Cerebrovascular Pathologies and Interventions
		Spine Surgeries
		When Macro-scale 3D Printing Meets Nanotechnology
	Challenges of 3D Printing in Neuroscience: Ethical and Safety Concerns
		Ethical Concerns: Ownership and Cells
		Safety
		Societal Questions
	The Future of 3D Printing in Neuroscience
	The Future of 4D Printing in Neuroscience
	Glossary of Terms, Abbreviations, and Acronyms
	References
44: Nano-Neurosurgery: Nanoparticle-Guided Strategies
	Introduction
	Nanotools for Neurosciences
		Bioimaging Nanotools
		Nanoparticles
		Nanoplatforms for Multimodal Neuroimaging
	Nanotools for Neural Probing of Brain Function
		Nanowires and Arrays
		Nano-Modified Microelectrode Arrays (MEAs)
	Nano-Grafted Neuromodulation Strategies
		Monomodal Nano-Neuromodulations
		Cross-Modal Nano-Neuromodulations
	Surgical Theranostics for Nano-Neurooncology
	Nano-Neurodegeneration Approaches
	Conclusion and Future Perspectives
	References
45: Food and Drug Administration Regulatory Framework for Nanodrugs and Nanodevices and the Combination
	In memory of Warren S. Grundfest Introduction
	510(K) and PMA Process, Device Classification, and Marketing
	National Nanotechnology Initiative
		Objectives of National Nanotechnology Initiative
	Preclinical Considerations
		Effects That Nanomaterials Can Impart on the Rest of a Formulation
	Biological Impact on Physicochemical Properties
	Biodistribution Studies
	Analyzing Nanoparticle Size
		mRNA Vaccine Technology
	Challenges in Characterization: Consistency Across Laboratories
	Constraints in Defining Nanotechnology, Nanomedicine, Nanoneuroscience, and Nanoneurosurgery
	FDA’S Approach to the Regulation of Nanotechnology
	Case Study
	Case Study
	Current Challenges Faced
	Conclusion
	References
46: Nanoneuroscience and Nanoneurosurgery: A Key Component of Presidential Brain Mapping and Cancer Moonshot, Neurotechnology and Brain Mapping Day Policy Initiatives
	Introduction
	The Problem to Be Addressed
		The National Alliance for NanoBioElectronics (NANBE) in Brain Mapping
		National Network for Human Brain and Specimen Banks (NNHBSB)
		National Data Repository and Analysis for Neuroscience (NDRAN)
	Purpose
	Significance of the Proposed Approach and Its Impact on the Field of Nanoneurosurgery and Nanoneuroscience and Brain Mapping
	Policy Programs and Initiatives Promulgated by the Society for Brain Mapping and Therapeutics
		Neuroscience20
	Brain Mapping Day in Parliaments across The Globe
	Brain Mapping Day at the California State Assembly
	Brain Research Day at the Canadian Parliament
	Brain Mapping Day at the Australian Parliament
	Brain Research Day at the Brazilian Parliament
	National Center for NanoBioElectronics
	Cancer Moonshot Initiative
	Conclusion
	References
Index