Engel’s Neurobiology of the Epilepsies

 

Description:

Neurobiology of the Epilepsies – From Epilepsy: A Comprehensive Textbook, 3rd Edition, provides a concise, up-to-date review of basic sciences and the latest research advances in epilepsy. Ideal for general neurologists and neurosurgeons, epilepsy/clinical neurophysiology specialists, basic scientists, clinical researchers, and other health care providers with an interest in epilepsy, this new volume by Drs. Istvan Mody, Hal Blumenfeld, Jerome Engel, Jr., Asla Ptkänen, Ivan Soltesz, and Annamaria Vezzani offers comprehensive, authoritative coverage of this critical and complex area of the field. 

 

Table of Contents:

 

Section 1 • Neurons and Their Circuits Relevant to Epilepsies

1 Transcriptional Channelopathies in Genetic and Acquired Epilepsies

TRANSCRIPTIONAL CHANNELOPATHIES

TRANSCRIPTIONAL REGULATION OF VOLTAGE-GATED ION CHANNELS LEADING TO GENETIC EPILEPSIES

Voltage-Gated K+ Channelopathies

Voltage-Gated Na+ Channelopathies

Voltage-Gated Ca2+ Channelopathies

HCN Ion Channelopathies

TRANSCRIPTIONAL REGULATION OF LIGAND-GATED ION CHANNELS LEADING TO GENETIC EPILEPSIES

NMDA Receptor Channelopathies

GABA Receptor Channelopathies

Nicotinic Acetylcholine Receptor Channelopathies

TRANSCRIPTIONAL CHANNELOPATHIES IN ACQUIRED EPILEPSIES

GABAA Receptor Alterations in Hippocampal Dentate Granule Cells in Multiple Experimental TLE Models

HCN Channel Alterations in Hippocampal CA1 Pyramidal Neurons in Multiple Experimental TLE Models

Cav3.2 Channel Upregulation in Hippocampal CA1 Pyramidal Neurons in an Experimental TLE Model

Potential for Therapy in Acquired Transcriptional Channelopathies

SUMMARY

REFERENCES

2 Principal Cell Heterogeneity in Malformations of Cortical Development and Acquired Epilepsy

INTRODUCTION

CORTICAL DEVELOPMENT AND MALFORMATIONS

Mispositioning of Neurons

Abnormal Cellular Development

NONUNIFORM COMPUTATIONAL MODULES FOR PARALLEL PROCESSING AND PRINCIPAL CELL HETEROGENEITY: INSIGHTS FROM THE HIPPOCAMPUS

PYRAMIDAL CELL HETEROGENEITY AND LOCAL MICROCIRCUITS IN THE HIPPOCAMPUS

PRINCIPAL CELL HETEROGENEITY IN THE DG IN CHRONIC TEMPORAL LOBE EPILEPSY

CONCLUSIONS AND OUTLOOK

ACKNOWLEDGMENTS

REFERENCES

3 Mechanisms of Neuronal Excitation Leading to Synchrony

INTRODUCTION

MEASURING NEURAL SYNCHRONY: THE IMPORTANCE OF TECHNICAL LIMITATION AND PERSPECTIVE

SYNAPTIC MECHANISMS FOR SYNCHRONIZATION: RECURRENCE

SYNAPTIC MECHANISMS FOR SYNCHRONIZATION: DISINHIBITION

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: INTRINSIC PROPERTIES

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: EXTRACELLULAR COMPARTMENT

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: EPHAPTIC COUPLING

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: GAP JUNCTION COUPLING

FUTURE OUTLOOK

REFERENCES

4 Interneuron Diversity in Epilepsy: Challenges and Promise

INTRODUCTION

OVERVIEW OF THE NORMAL DIVERSITY OF INTERNEURONS

Interneurons Innervating Principal Cell Soma or Axon Initial Segments

Interneurons Innervating Principal Cell Dendrites

Interneurons Innervating Other Interneurons

WHAT INTERNEURONS DEGENERATE IN ACQUIRED EPILEPSY?

WHAT ARE THE FUNCTIONAL CONSEQUENCES OF INTERNEURON LOSS?

HOW DO SURVIVING INTERNEURONS ADAPT IN THEIR STRUCTURE AND FUNCTION?

Functional Impairment of Surviving Interneurons

Overexpression of Neuropeptides and Glutamate Decarboxylases in Surviving Interneurons

Sprouting and Reorganization of Surviving Interneurons

WHAT ARE THE ROLES OF SURVIVING INTERNEURONS IN EPILEPSY?

Effects of Selectively Modulating Interneuron Activity

Monitoring Interneuron Activity Prior to and During Seizure Activity

WHAT IS THE POTENTIAL FOR INTERNEURON-BASED TREATMENT OF EPILEPSY?

Transplantation of Interneurons for the Treatment of Epilepsy

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

5 Mechanisms of Neuronal Inhibition Leading to Synchrony

INTRODUCTION

AN OVERVIEW OF INTERNEURONAL CLASSES AND CONNECTIVITY IN CORTICAL NETWORKS

PHYSIOLOGIC SYNCHRONIZATION

DETERMINANTS OF GABA CURRENT: INTRA- AND EXTRACELLULAR CHLORIDE

DYNAMIC CHANGES IN GABAERGIC FUNCTION

GABAERGIC INFLUENCES IN EPILEPTIC DISCHARGES

CHARACTERISTICS OF CELLULAR RECRUITMENT TO SEIZURES

REFERENCES

6 Neurons and Circuits During Brain Development

INTRODUCTION

DEVELOPMENTAL CHANGES IN NEURONAL PROPERTIES

GAP-JUNCTION CONNECTIONS

EXCITATORY SYNAPTIC CONNECTIONS

Local and Long-Range Connections

Functional Properties of Developing Excitatory Synapses

INHIBITORY CIRCUITS

Delayed Recruitment of Perisomatic Inhibition

Depolarizing Actions of GABA

Actions of GABA in Vivo

EARLY NETWORK ACTIVITY PATTERNS

Correlated Activity Mediated by Gap Junctions

Delta Waves

Early Gamma and Spindle-Burst Oscillations

CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

7 Metabolism, Reactive Oxygen Species, and Epilepsy

INTRODUCTION

Neuronal–Glial Metabolism

REACTIVE OXYGEN SPECIES IN EPILEPSY

MITOCHONDRIA AS A SOURCE AND TARGET OF ROS IN EPILEPSY

NOX ENZYMES AS SOURCES OF ROS IN EPILEPSY

PHARMACOLOGIC REDOX-BASED APPROACHES FOR EPILEPSY AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

8 Dendritic Mechanisms of Excitability

INTRODUCTION

Basic Mechanisms of Dendritic Integration

ALTERED DENDRITIC MORPHOLOGY AND PASSIVE MEMBRANE PROPERTIES IN EPILEPSY

ACTIVE MECHANISMS IN DENDRITES AFFECTING PROPAGATION OF VOLTAGE SIGNALS

Voltage- and Ca2+-Gated K+ Channels

Dendritic h-currents

Voltage-Gated Na+ Channels

ACTIVE MECHANISMS IN DENDRITES: DENDRITIC SPIKES

ALTERED DENDRITIC ELECTROPHYSIOLOGY IN EPILEPSY

Epilepsy-Related Changes in Dendritic Kv4.2 Channels

Epilepsy-Related Changes in Dendritic HCN Channels

Changes in Dendritic T-Type Currents Mediated by CaV3.2 Channels

Epilepsy-Related Changes in KCa3.1 Channels

Mechanisms of Dendritic Integration Across Species—Mouse to Human

ROLE OF ACTIVE DENDRITIC INTEGRATION IN VIVO

Outlook

REFERENCES

9 Thalamocortical Organization and Function: New Insights and Implications for Epilepsy

INTRODUCTION

ANATOMICAL AND FUNCTIONAL OVERVIEW OF THE THALAMUS

SINGLE-CELL ANALYSES ESTABLISH A HIGH-RESOLUTION FRAMEWORK OF THE THALAMUS

Classification of TC Relay Nuclei

In Search of Molecular Markers for the nRT

MAPPING MOLECULAR PROPERTIES WITH CIRCUIT PROPERTIES REVEALS NEW PATHWAYS

Intra-nRT Connectivity

Insights from Dissecting the Role of nRT in Spindle Oscillations: Can nRT Spindles Elucidate Seizures?

NEW INSIGHTS ON THE ROLE OF nRT IN TC SEIZURE DYNAMICS

CONCLUDING REMARKS

Molecular Insights

Electrophysiologic Insights

Circuit Insights

REFERENCES

10 Mechanisms of Focal Seizure Initiation and Propagation

INTRODUCTION

ELECTROPHYSIOLOGIC SIGNATURES OF FOCAL SEIZURES

Clinical EEG Assessment

Electrographic Seizure-Onset Patterns

High-Frequency Activity as a Biomarker of Seizure-Generating Sites

Infra-Slow Activity at Seizure Onset

NEURONAL ACTIVITY IN SEIZURE INITIATION AND MAINTENANCE

Ictal Neuronal Firing Patterns

Neuronal Cell-Type–Specific Activity

Mechanisms Underlying the Seizure Transition

Dysregulated Chloride Homeostasis

Interneuron Depolarization Block

Astrocyte-Mediated Excitation

Spatial Structure of Human Seizures

The Dual-Territory Hypothesis: Ictal Core and Penumbra

Cross-Scale Seizure Effects

Epileptic Networks

CONCLUDING REMARKS

REFERENCES

11 Seizures and Networks in the Human Focal Epilepsies: Beyond the Animal Models

INTRODUCTION

FOCAL SEIZURE–ONSET PATTERNS

LESION-SPECIFIC ICTAL PATTERNS

REGION-SPECIFIC ICTAL PATTERNS

THE EPILEPTOGENIC NETWORKS

CONCLUSIONS

REFERENCES

12 Temporal Coordination: A Key to Understand Cognitive and Behavioral Deficits in Epilepsy

INTRODUCTION: LOSING THE BEAT

COGNITIVE AND BEHAVIORAL IMPAIRMENTS IN EPILEPSY

GENERAL CONTRIBUTORS OF COGNITIVE COMORBIDITIES

PHYSIOPATHOLOGIC FEATURES OF EPILEPSIES

The Case of TLE

The Case of Epilepsies of Genetic Origin

Network Mechanisms Underlying Cognitive Impairment in Epilepsy

Alterations of Neuronal Network Dynamics and Computation

Impact on High-Level Cognitive Representations

RHYTHMOPATHIES AND EPILEPSY

θ Oscillations and Epilepsy

γ Oscillations and Epilepsy

High-Frequency Oscillations in Epilepsy

From Interneuropathies to Rhythmopathies

CONCLUSIONS

REFERENCES

13 Epilepsy and Consciousness

INTRODUCTION

THE DIMENSIONS OF CONSCIOUSNESS IN SEIZURES

ESTIMATION OF CONSCIOUSNESS DURING SEIZURES

IMPAIRED CONSCIOUSNESS IN GENERALIZED SEIZURES

Absence Seizures

IMPAIRED CONSCIOUSNESS IN FOCAL SEIZURES

Extratemporal Lobe Seizures

Mechanisms

Insights from Animal Models

THERAPEUTIC APPROACHES

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

Section 2 • Technical and Conceptual Advances for Epilepsy Research

14 Activating and Recording Neuronal Ensembles

INTRODUCTION

ACTIVATING NEURONAL ENSEMBLES

Electrical Stimulation

Optogenetic Stimulation

Chemogenetic Activation

RECORDING NEURONAL ENSEMBLES

Wireless Telemetry

Imaging Techniques

CONSIDERATIONS AND PERSPECTIVES

REFERENCES

15 Optical Recording of Neuronal Excitability and Synchrony with Genetically Encoded Calcium and Voltage Indicators

INTRODUCTION

ADVANCES IN FLUORESCENCE MICROSCOPY

Miniaturized Epifluorescence Microscopy

Genetically Encoded Probes for Recording Neuronal Excitability

Calcium Indicators

Voltage Sensors

METHOD OF DELIVERY

Viruses

Transgenic Animals

Electroporation

RECORDING NEURAL EXCITABILITY AND SYNCHRONY WITH GENETICALLY ENCODED FLUORESCENT INDICATORS IN THE CONTEXT OF EPILEPSIES

ACKNOWLEDGMENTS

REFERENCES

16 Fast Rhythms in Epilepsies

INTRODUCTION

DEFINITION/DESCRIPTION OF FAST RHYTHMS

FAST RHYTHMS IN THE NORMAL BRAIN

FAST RHYTHMS IN THE EPILEPTIC BRAIN

Pathologic Gamma Activity

Cellular and Network Mechanisms of Epileptic Ripples

Cellular and Network Mechanisms of Epileptic Fast Ripples

Mechanisms of Very-High HFOs

Regional Properties of Pathologic HFOs

SIGNIFICANCE OF FAST RHYTHMS

HFOs in Epileptogenesis

HFOs as a Marker of Seizure Susceptibility

FUTURE DIRECTIONS

REFERENCES

17 Miniaturized Microscopy as a Tool to Track Neuronal Population Dynamics in Epilepsy Models

INTRODUCTION

Brief History of Imaging IN BEHAVING ANIMALS

MINIATURE MICROSCOPY

CURRENT TOOLS AND FEATURES

Electrowetting Lenses

Dual-Channel Microscopes

Optogenetics

Wide-Field Imaging

Neurovascular Coupling

Volumetric Imaging

Wireless and Wire-Free

Electrophysiology

Simultaneous Behavior Tracking/Readout

DATA ANALYSIS

FUTURE INNOVATION OF MINIATURE MICROSCOPY

Wireless Power Delivery and Data Transmission

Close-Loop Experiments

Fast Imaging of Voltage Sensors

Lensless Imaging

STUDYING EPILEPSY WITH MINISCOPES

SUMMARY

REFERENCES

18 Seizure Control Through Closed-Loop Systems

INTRODUCTION

CLOSED-LOOP INTERVENTIONS: AN OVERVIEW

Example Potential Signals for Seizure Detection

Closed-Loop Interventions Are Not Limited to Electrical Stimulation Approaches

Closed-Loop Approaches Are Not Limited to On-Demand Interventions

ADVANTAGES OF CLOSED-LOOP SYSTEMS

CURRENT CLOSED-LOOP INTERVENTIONS IN EPILEPSY

Responsive Neurostimulation System

On-Demand Stimulation of the Vagus Nerve

Biofeedback

CLOSED-LOOP INTERVENTIONS IN EPILEPSY: ANIMAL STUDIES PROVIDE INSIGHT AND INFORM POTENTIAL FUTURE APPROACHES

Closed-Loop Approaches in Absence Epilepsy Models

Closed-Loop Approaches in Temporal Lobe Epilepsy Models

Closed-Loop Gene Therapy via eGluCl

FUTURE DIRECTIONS

CONCLUSIONS

REFERENCES

19 Biomarkers

INTRODUCTION

SUSCEPTIBILITY/RISK BIOMARKERS

Genetic Risk Biomarkers

Blood/CSF Risk Biomarkers

Neurophysiology Risk Biomarkers

Neuroimaging Risk Biomarkers

DIAGNOSTIC BIOMARKERS

Diagnostic Genetic Biomarkers

Diagnostic Blood/CSF Biomarkers

Diagnostic Neurophysiologic Biomarkers

Diagnostic Imaging Biomarkers

PROGNOSTIC BIOMARKERS

Prognostic Genetic Biomarkers

Prognostic Blood/CSF Biomarkers

Prognostic Neurophysiologic Biomarkers

Prognostic Imaging Biomarkers

MONITORING AND PREDICTIVE BIOMARKERS/SURROGATE ENDPOINTS

Predictive Genetic Biomarker

Predictive Blood/CSF Biomarkers

Predictive Neurophysiology Markers

Predictive Imaging Biomarkers

CONCLUSIONS

REFERENCES

20 Comorbidities as Prognostic Factors for Epileptogenesis

INTRODUCTION

BEHAVIORAL AND COGNITIVE METHODS USED TO ASSESS COMORBIDITIES IN ANIMAL MODELS OF ACQUIRED EPILEPSY

Comorbidities in Animal Models of Acquired Epilepsy

COMORBIDITIES AND SEIZURE THRESHOLD AS PROGNOSTIC FACTORS FOR EPILEPTOGENESIS

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

21 Use of Human Pluripotent Stem Cells in Epilepsy Research

INTRODUCTION

IPSC Methods Relevant to Epilepsy Studies

INVESTIGATION OF EPILEPSY PHENOTYPES IN 2D CULTURES

Brain Organoids for Epilepsy Research

Exploring SUDEP Mechanisms with iPSCs

CHALLENGES AND FUTURE DIRECTIONS

CONCLUSIONS

REFERENCES

Section 3 • Other Contributors to Excessive Synchrony and Seizures

22 Novel Roles of Myelination in Neural Circuit Plasticity and Implications for Epilepsy

INTRODUCTION

ROLES OF MYELIN IN THE CENTRAL NERVOUS SYSTEM

Role of Myelination in Regulating Timing of Neuronal Signals

DEVELOPMENTAL MYELINATION AND THE LIFE CYCLE OF THE OLIGODENDROCYTE

Oligodendrocyte Precursor Cells

Premyelinating Oligodendrocytes

Myelin Wrapping and Compaction

Neuronal Activity in the Regulation of Myelination

How Does Neuronal Activity Influence Myelination?

MOLECULAR MECHANISMS OF NEURONAL ACTIVITY-DEPENDENT MYELINATION

Neuronal Signals and Activity-Dependent Myelination

Translating Neuronal Signals Into OL Responses: Intracellular Calcium

Calcium-Regulation of OL Cell Biology: Mechanistic Insight Into Activity-Dependent Myelination

INTERNEURON MYELINATION

OPEN QUESTIONS

Structure and Function of Neuron-OPC Synapses

Molecular Mechanisms Regulating Activity-Dependent Myelination

Functional Relevance of Activity-Dependent Myelination in Regulating Neural Circuit Function and Behavior

Function of PV Myelin

Role of Myelin and Myelin Pathology to Epilepsy

CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

23 Role of Dysfunctional Astrocytes in Epileptogenesis

INTRODUCTION

BASIC PHYSIOLOGY OF “NORMAL” ASTROCYTES

Membrane Physiology

Astrocyte Metabolism and Synaptic Activity

ASTROCYTE DYSFUNCTIONS CONTRIBUTE TO INITIATION AND PROGRESSION OF EPILEPSY

Reactive Astrocytes May Generate Seizure Activity

Altered K+ Channels and Water Channels in Epilepsy

Loss of Astroglial Gap-Junction Coupling as a Key Mechanism in Initiation and Progression of TLE

Altered Glutamate Homeostasis in Epilepsy

Astrocyte Ca2+ Signaling in Epilepsy

CONCLUSIONS AND PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

24 Neurovascular Inflammation in Epilepsy

INTRODUCTION

EVIDENCE FOR PERSISTENT NEUROINFLAMMATION AND ITS DEFECTIVE RESOLUTION IN EPILEPSY

NEUROINFLAMMATORY SIGNALS IMPLICATED IN EXPERIMENTAL EPILEPSY

The IL-1β System

The Prostanoid Cascade: The Focus on MAGL and COX-2

Specialized Proresolving Molecules

MECHANISMS OF HYPEREXCITABILITY

CEREBROVASCULAR PERMEABILITY AND PERIVASCULAR INFLAMMATION DURING SEIZURES

PERIPHERAL INFLAMMATION AND EPILEPSY: HUMAN AND EXPERIMENTAL EVIDENCE

DOES PRE-EXISTING INFLAMMATION ENABLE SEIZURES?

CONCLUSIONS ON THERAPEUTIC PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

25 The Blood–Brain Barrier and Epilepsies

INTRODUCTION

BBB DYSFUNCTION FOLLOWING BRAIN INSULTS

BBB DYSFUNCTION AND EPILEPSIES

BBB Dysfunction and Mechanisms Underlying Epileptogenesis

BBB-TARGETED THERAPIES: A NEW OPPORTUNITY IN THE PREVENTION AND TREATMENT OF EPILEPSY?

REFERENCES

26 The mTOR Pathway in Epileptogenesis

INTRODUCTION

mTOR in Animal Models of TSC

mTOR in Animal Models of Other Genetic and Acquired Epilepsies

CLINICAL TRANSLATION OF mTOR INHIBITORS IN EPILEPSY AND TSC

CONCLUSIONS AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

27 Epigenetic Mechanisms

INTRODUCTION

OVERVIEW: EPIGENETICS, GENE EXPRESSION, AND CHROMATIN STRUCTURE

Gene Expression and Protein Production

DNA Organization and Epigenetic Modifications

CORE EPIGENETIC MECHANISMS CONTROLLING GENE EXPRESSION

DNA Methylation

Histone Posttranslational Modifications and Histone Variants

Noncoding RNA

Other Mediators of Epigenetic Processes

EPIGENETIC MECHANISMS IN EPILEPSY

DNA Methylation in Epilepsy

Histone Modifications in Epilepsy

Noncoding RNAs in Epilepsy

EPILEPSY-ASSOCIATED GENES WITH EPIGENETIC FUNCTIONS

INTERACTIONS AND INTERDEPENDENCE IN EPIGENETICS: ADDING A LAYER OF COMPLEXITY

CELL SPECIFICITY IN EPIGENETICS: AN ONGOING CHALLENGE

How Do Epigenetic Processes Favor or Protect Against Neuronal Excitability and Seizures?

Metabolically Controlled Epigenetic Mechanisms in Epilepsy

DIAGNOSTIC IMPLICATIONS OF EPIGENETICS RESEARCH IN EPILEPSY

THERAPEUTIC IMPLICATIONS AND LIMITATIONS

CHAPTER SUMMARY: RESEARCH PROSPECTS AND CHALLENGES

REFERENCES

28 Purinergic Signaling in Epilepsy

OVERVIEW: EVOLUTIONARY LOGIC OF PURINERGIC REGULATION. WHY IS IT SO DIFFERENT COMPARED TO ANTISEIZURE DRUGS?

ADENOSINE AND ATP METABOLISM

THE ADENOSINE KINASE HYPOTHESIS OF EPILEPTOGENESIS

THE RECEPTORS

DYSREGULATION OF THE PURINERGIC SYSTEM IN EPILEPSY

P2 Receptor Expression Changes

PURINERGIC TREATMENT OPTIONS

Targeting P2 Receptors

Targeting Adenosine Metabolism

Adenosine Augmentation Strategies

SUMMARY AND CONCLUSIONS

REFERENCES

29 Neurotrophic Factors

INTRODUCTION

Neurotrophic Factors: Molecular Effectors of Activity-Induced Plasticity

NEUROTROPHINS

Brain-Derived Neurotrophic Factor

Nerve Growth Factor

Neurotrophin 3 and Neurotrophin 4

GLIAL-DERIVED NEUROTROPHIC FACTORS

Glial Cell Line-Derived Neurotrophic Factor

FIBROBLAST GROWTH FACTORS

Fibroblast Growth Factor 2

PERSPECTIVE AND CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

30 Neurogenesis in Epilepsy

INTRODUCTION

MECHANISMS OF ADULT HIPPOCAMPAL NEUROGENESIS IN RODENT HIPPOCAMPUS

EVIDENCE FOR ADULT HIPPOCAMPAL NEUROGENESIS IN HUMANS

ACTIVITY-DEPENDENT NEUROGENESIS IN PHYSIOLOGIC AND PATHOLOGIC CONTEXTS

A WIDE VARIETY OF EPILEPTOGENIC INSULTS DISRUPT NEUROGENESIS

FUNCTIONAL SIGNIFICANCE OF ABNORMAL HIPPOCAMPAL GRANULE CELLS

Pathologic Roles of Adult-Generated Granule Cells

Beneficial Roles of Adult-Generated Granule Cells

NEUROGENESIS IN THE DEVELOPMENT OF TEMPORAL LOBE EPILEPSY

Abnormal Granule Cells Are Sufficient to Cause Epilepsy

Ablating Adult-Generated Granule Cells Is Antiepileptogenic

TARGETING NEUROGENESIS AS A THERAPEUTIC STRATEGY TO TREAT EPILEPSY

Early Intervention

Late Intervention

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

31 Somatic Mosaicism in Focal Malformations of Cortical Development

INTRODUCTION

CLINICAL AND NEUROPATHOLOGIC FEATURES OF FOCAL MCDS

BRAIN SOMATIC MOSAICISM

SOMATIC VARIANTS IN FOCAL MCDS

mMCD, MOGHE and FCD Type 1

FCD Type 2 and HME

EPIGENETIC SIGNATURES IN CORTICAL MALFORMATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

32 The Microbiota–Gut–Brain Axis and Epilepsy

INTRODUCTION

THE MICROBIOTA–GUT–BRAIN AXIS

THE MICROBIOTA–GUT–BRAIN AXIS IN BRAIN DEVELOPMENT

THE GUT MICROBIOME IN EPILEPSY

THE GUT MICROBIOME AND THE KETOGENIC DIET IN EPILEPSY

THE IMPACT OF DRUG TREATMENT ON THE GUT MICROBIOTA

POTENTIAL MICROBIAL THERAPEUTIC TARGETS FOR EPILEPSY

Conclusions and Future Perspectives

ACKNOWLEDGMENTS

References

Index

 

An aparitie	25 Oct. 2022
Autor	Jerome Engel, Jr., istvan mody
Dimensiuni	213 x 276 mm
Editura	LWW
Format	Paperback
ISBN	9781975194215
Limba	Engleza
Nr pag	384
Versiune digitala	DA