Jasper's basic mechanisms of the epilepsies:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
New York, NY
Oxford Univ. Press
2012
|
| Ausgabe: | 4. ed. |
| Schriftenreihe: | Contemporary neurology series
80 |
| Schlagworte: | |
| Online-Zugang: | Klappentext Inhaltsverzeichnis |
| Beschreibung: | LVII, 1199 S. Ill., graph. Darst. |
| ISBN: | 9780199746545 0199746540 |
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| 245 | 1 | 0 | |a Jasper's basic mechanisms of the epilepsies |c ed.: Jeffrey L. Noebels ... |
| 246 | 1 | 3 | |a Basic mechanisms of the epilepsies |
| 250 | |a 4. ed. | ||
| 264 | 1 | |a New York, NY |b Oxford Univ. Press |c 2012 | |
| 300 | |a LVII, 1199 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 1 | |a Contemporary neurology series |v 80 | |
| 650 | 7 | |a Epilepsie |2 gtt | |
| 650 | 7 | |a Épilepsie - Congrès |2 ram | |
| 650 | 4 | |a Épilepsie - Diagnostic | |
| 650 | 4 | |a Épilepsie - Traitement | |
| 650 | 2 | |a Épilepsie | |
| 650 | 4 | |a Epilepsy | |
| 650 | 4 | |a Epilepsy |v Congresses | |
| 650 | 4 | |a Pathology, Cellular |v Congresses | |
| 650 | 4 | |a Pathology, Molecular |v Congresses | |
| 650 | 0 | 7 | |a Epilepsie |0 (DE-588)4015035-5 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4143413-4 |a Aufsatzsammlung |2 gnd-content | |
| 655 | 7 | |0 (DE-588)1071861417 |a Konferenzschrift |2 gnd-content | |
| 689 | 0 | 0 | |a Epilepsie |0 (DE-588)4015035-5 |D s |
| 689 | 0 | |5 DE-604 | |
| 700 | 1 | |a Noebels, Jeffrey L. |e Sonstige |4 oth | |
| 700 | 1 | |a Jasper, Herbert H. |d 1906-1999 |e Sonstige |0 (DE-588)124328784 |4 oth | |
| 830 | 0 | |a Contemporary neurology series |v 80 |w (DE-604)BV000898796 |9 80 | |
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| 856 | 4 | 2 | |m Digitalisierung UB Regensburg |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025464183&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-025464183 | ||
Datensatz im Suchindex
| _version_ | 1804149750543417344 |
|---|---|
| adam_text | Contents
( oiitriliiitiirs 1
SECTION
1
INTRODUCTION
1.
THE NEXT DECADE OF RESEARCH IN THE RASIC MECHANISMS
OF THE EPILEPSIES
3
Jeffrey
L.
S oehels, Massimo
Avoli.
Michael A. Rogawski, Richard V.
Olsen,
and Antonio V.
Delgado-Escueta
SECTION
1:
INTRODUCTION
3
SECTION
2:
FUNDAMENTALS OF
NEURONAL
EXCITABILITY HELENA NT
TO SEIZURES AND EPILEPSY
4
SECTION
3:
MECHANISMS OF SEIZURE SUSCEPTIBILITY
AND EPILEPTOCENESIS
5
SECTION
4:
EPILEPSY CKNES AND DEN EI.OPMENT
fi
SECTION
5:
EPILEPSY THERAPEUTICS
10
CLOSINC SUMMARY
11
2.
HERBERT H. JASPER AND THE BASIC MECHANISMS OF THE
EPILEPSIES
12
Massima Avoli
THE EARLY YEARS
12
NVORK AT THE MONTREAL NEUROLOGICAL INSTITUTE
14
THE FOUNDING OF IBRO AND THE BME PROJECT
19
MOVING TO THE OTHER SIDE OF THE MOUNTAIN
(MONT ROYAL, OF COURSE!)
20
HERBERT JASPERS LATE YEARS
20
APPENDIX: ORIGINAL CURRICULUM
VITAE
OF DR. H. JASPER,
DATED APPROXIMATELY
1954 22
3.
WHY—AND HOW—DO WE APPROACH BASIC EPILEPSY RESEARCH?
24
Philip A. Schwarizkroin
WHAT DO WE MEAN BY BASIC RESEARCH?
25
Exploration and Discovery
·
Hypothesis Testing
·
Invention and Technological Advancement
WHAT CAN WE ACCOMPLISH BY ENGAGING IN BASIC RESEARCH?
26
Knowledge for the Sake of Knowledge
·
Control
·
Quality of
Ufe
xi
xii Contents
WHY DO BASIC EPILEPSY RESEARCH?
27
Because It s Interesting
·
Because It Sheds Light on General Brain Function
·
Because It Offers
Real Opportunities for Research Career Development
·
Because It May Lead to Development of
Better Treatments and Cures
HOW DO WE CHOOSE AND PRIORITIZE RESEARCH GOALS?
29
Identification of Important Problems
·
Understanding Basic Mechanisms versus Empirical
Testing
·
Detailed Analyses versus the Big Picture
WHAT APPROACHES—CONCEPTUAL OR TECHNICAL—ARE LIKELY
TO YIELD SIGNIFICANT RESULTS?
31
Conceptual Goals
·
Technical Approaches
·
Model Development
CONCLUDING THOUWGHTS
35
SECTION
2
FUNDAMENTALS OF
NEURONAL
EXCITABILITY
RELEVANT TO SEIZURES AND EPILEPSY
4.
VOLTAGE-GATED NA+ CHANNELS
:
STRUCTURE, FUNCTION,
AND PATHOPHYSIOLOGY
41
Massimo
Mantegazza and William A. Catterall
NA+ CHANNEL SUBUNIT STRUCTURE
41
Na+ CHANNEL GENES
42
MOLECULAR BASIS OF Na+ CHANNEL FUNCTION
44
THREE-DIMENSIONAL STRUCTURE OF Na+ CHANNELS
46
EXPRESSION, LOCALIZATION, AND FUNCTION OF Na+ CHANNEL
SUBTYPES IN THE NERVOUS SYSTEM
46
Na+CHANNEL PHARMACOLOGY
48
Na+ CHANNEL AND EPILEPSY
49
GENETIC Na+ CHANNELOPATHIES
49
FUTURE DEVELOPMENTS AND CHALLENGES
50
5.
POTASSIUM CHANNELS (INCLUDING KCNQ) AND EPILEPSY
55
Edward C.
Cooper
K+ CHANNELS: A DIVERSE SUPERFAMILY DERIVED FROM AN
EXTRAORDINARILY USEFUL TEMPLATE
56
K* Channel Variant
1: Two-Transmembrane (2TM) ·
Structural Variant
2:
Two-Pore
(4TM)
·
Structural Variant
3:
Voltage-Gated (6TM)
·
Structural Variant
4:
Non-Pore Forming
Accessory Subunits
KCNQ CHANNELS: FROM CHANNELOPATHY TO NOVEL THERAPY
60
KCNQ CHANNELS AND BEYOND: PROSPECTS FOR FUTURE POTASSIUM
CHANNEL STUDIES IN EPILEPSY RESEARCH
62
Contents xiii
6.
VOLTAGE-GATED
CALCIUM
CHANNELS IN
EPILEPSY
66
Stuart
M.
Cain and
Terranee
P. Snutch
CALCIUM CHANNEL NOMENCLATURE
67
CALCIUM CHANNEL BIOPHYSICAL PROPERTIES
67
CALCIUM CHANNELS AND EXCITABILITY
68
Т
-Type
Channels and Excitability
·
HVA Calcium Channels and Excitability
CALCIUM CHANNELS IN ABSENCE EPILEPSY
70
Т
-Type
Calcium Channels in the Thalamocortical Network and Absence Seizures
·
Calcium
Channels in Human Epilepsy
·
Т
-Type
Calcium Channels in Absence Epilepsy Animal
Models
·
HVA Channels in Absence Epilepsy Animal Models
·
Calcium Channel Ancillary
Subunits in Absence Epilepsy Models
CALCIUM CHANNELS IN TEMPORAL LOBE/COMPLEX PARTIAL EPILEPSY
75
Т
-Type
Calcium Channels in the
Pilocarpine
Model of Temporal Lobe Epilepsy/Complex Partial
Epilepsy
·
Т
-Type
Channels in the Electrical Kindling Model of
Limbie
Epilepsy
·
HVA Channels
in Electrical Kindling Models of
Limbie
Epilepsy
·
CaN.2.3 R-Type Channels in
Kainie
Acid-Induced
Limbie
Epilepsy Model
CALCIUM CHANNELS IN GENERALIZED CONVULSIVE SEIZURES
78
HVA Calcium Channels in Genetic Epilepsy-Prone Rats
·
Generalized Seizures in
Сіц.2.3
Transgenic
Mice
·
Calcium Channel Ancillary Subunits in Genetic Convulsive Animal Models
CONCLUSIONS
78
7.
HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED (HCN)
ION CHANNELOPATHY IN EPILEPSY
85
Nicholas P. Poolos
HCN CHANNEL BIOPHYSICAL PROPERTIES
86
HCN CHANNEL EFFECTS ON
NEURONAL
EXCITABILITY
87
CONTRIBUTION OF HCN CHANNELS TO EPILEPSY
89
Evidence for Human HCN Channelopathy
·
HCN Channels in Animal Models of Genetic
Epilepsy
·
HCN Channel Downregularion in Animal Models of Acquired Epilepsy
·
Mechanisms of HCN Channel Downregulation in Acquired Epilepsy
·
Antiepileptic Drug
Actions on HCN Channels
CONCLUSIONS
93
8.
PHASIC GABA^MEDIATED INHIBITION
97
Enrico Cherubini
GABA^-MEDIATED IPSCS: PRESYNAPTIC REGULATION
98
Source of
GABA
·
Regulation of
GABA
Release by Presynaptic Intracellular Calcium
Stores
·
Regulation of
GABA
Release by Presynaptie
GABAĄ
and GABAB Receptors
DYNAMICS OF
GABA
TRANSIENTS IN THE SYNAPTIC CLEFT
99
GABA
Transients May Regulate Synaptic Variability
·
GABA
Transporters
xiv Contents
GABA^MEDIATED IPSCS: POSTSYNAPTIC REGULATION 101
GABAA
Receptors
·
Permeability of
GABAA
Receptor
Channels ·
Heterogeneity of GABAA
Receptors
·
GABAA Receptor Distribution
·
Modulation of GABAA Receptors
FUTURE PERSPECTIVES
106
9.
TONIC GABAA RECEPTOR-MEDIATED SIGNALING IN EPILEPSY 111
Matthew C. Walker and
Dimitri
M.
Kullmann
GABAA RECEPTOR SUBTYPES UNDERLYING TONIC CONDUCTANCES
112
FUNCTIONS OF TONIC GABAA RECEPTOR CURRENTS
113
TONIC INHIBITION IN THE HIPPOCAMPUS AND TEMPORAL LOBE
EPILEPSY
116
TONIC INHIBITION IN ABSENCE SEIZURES AND ABSENCE EPILEPSY
117
TONIC INHIBITION AS A TARGET FOR ANTIEPILEPTIC DRUGS
117
CONCLUSION
118
10.
GLUTAMATERGIC MECHANISMS RELATED TO EPILEPSY:
IONOTROPIC RECEPTORS
122
Raymond Dingledine
NOMENCLATURE
123
GLUTAMATE
RECEPTOR STRUCTURE
123
CONTROL OF RECEPTOR PROPERTIES
125
GLUTAMATERGIC MECHANISMS IN EPILEPSY
127
Astrocytic Release of
Glutamate
·
Impaired
Glutaminę
Cycle in Sclerotic Tissue
·
Special Role for
Kainate Receptors in Epilepsy
CHALLENGES AND OPPORTUNITIES
129
11.
GLUTAMATE
RECEPTORS IN EPILEPSY: GROUP I mGluR-MEDIATED
EPILEPTOGENESIS
132
Riccardo
Bianchi,
Robert
K S.
Wong, and Lisa
К
Merlin
THE mGluR MODEL OF EPILEPTOGENESIS
133
KEY FEATURES RELEVANT TO INDUCTION OF GROUP I
mGluR-DEPENDENT EPILEPTOGENESIS
134
Silent Induction
·
Group I mGluR Subtypes: mGluRl and mGluR5
·
NMDA Receptors
·
Protein
Synthesis
·
Phospholipase
С
·
Extracellular-Signal-Regulated Kinase
1/2 ·
Phospholipase
D
WHAT SUSTAINS THE ONGOING EXPRESSION OF THE GROUP I
mGluR-INDUCED ICTAL DISCHARGES?
136
Autopotentiation
·
Persistent Effects of Group I mGluR Activation
Contents xv
ENDOGENOUS
REGULATION
OF
GROUP
I mGluR-DEPENDENT
EPILEPTOGENESIS 137
FRAGILE
X SYNDROME: A CLINICAL CONDITION IN WHICH
HYPEREXCITABLE GROUP I mGluRS UNDERLIE A PHENOTYPE THAT
INCLUDES SEIZURES
139
ADDITIONAL CLINICAL CONDITIONS IN WHICH GROUP I mGluR
HYPEREXCITABILITY MAY PLAY A KEY ROLE
139
Alzheimer s Disease and Down Syndrome
·
Posttraumatic and Poststroke Epilepsy
12.
PLASTICITY OF
GLUTAMATE
SYNAPTIC MECHANISMS
143
J. Victor Nadler
STRENGTHENING OF RECURRENT EXCITATION
143
EXTRACELLULAR
GLUTAMATE
CONCENTRATION
145
Glutamate
Biosynthesis
·
Glutamate
Release
·
Conversion to
Glutaminę
·
Plasma Membrane Transport
GLUTAMATE
RECEPTORS
148
AMPA
Receptors
·
Ν Μ
DA Receptors
·
Kainate Receptors
·
Metabotropic
Glutamate
Receptors
SUMMARY AND FUTURE DIRECTIONS
153
13. NEURONAL
SYNCHRONIZATION AND THALAMOCORTICAL RHYTHMS
DURING SLEEP, WAKE, AND EPILEPSY
157
Igor Timofeev, Maxim Bazhenov,
Josée
Seigneur, and Terrence Sejiuncski
MECHANISMS OF
NEURONAL
SYNCHRONIZATION
158
Chemical Synaptic Mechanisms of Synchronization
·
Gap Junctions and
Synchronization
·
Ephaptic Interactions
·
Changes in Extracellular Ionic Concentrations
THALAMOCORTICAL OSCILLATIONS
161
Near-Steady or Infra-Slow Oscillation (<0.1 Hz)
·
Slow Oscillation
·
Delta Oscillation
·
Sleep
Spindle Oscillations
·
Beta-Gamma Oscillation
·
Ripples
·
Short- and
Long-Range
Synchrony
during Experimental Epilepsy
CONCLUSIONS
169
14.
LIMBIC NETWORK SYNCHRONIZATION AND TEMPORAL
LOBE EPILEPSY
176
John G.R. Jefferys,
Přemysl
Jiruska, Marco
de
Curtis, and Massimo
Avoli
MECHANISMS OF SYNCHRONIZATION DURING LIMBIC SEIZURES
177
Synaptic Mechanisms
·
Nonsynaptic Mechanisms
SEIZURE ONSET
182
SEIZURE TERMINATION
183
ROLES AND INTERACTIONS OF SPECIFIC LIMBIC AREAS IN SEIZURES
184
xvi Contents
NEUROBIOLOGY OF
TEMPORAL LOBE
EPILEPSY
184
Hippocampal
Sclerosis and Other Pathologies
· High-Frequeney
Oscillations
TARGETING
SYNCHRONY AS AN APPROACH TO THERAPY
186
CONCLUSIONS
186
15.
IMAGING OF HIPPOCAMPAL CIRCUITS IN EPILEPSY
190
Hajirne
Takáno
and Douglas A. Coulter
FUNCTIONAL IMAGING
191
Why Functional Imaging?
·
Spatial and Temporal
Resolution ·
Various Types of Functional
Imaging
·
Various Stimulation Methods in Imaging Studies
IMAGING THE EPILEPTIC BRAIN: REPRESENTATIVE EXAMPLES
196
Dentate Gyrus Gating Function
·
Calcium Imaging of Epileptiform Activity
CONCLUSIONS
199
16.
NORMAL AND PATHOLOGICAL HIGH-FREQUENCY OSCILLATIONS
202
Richard]. Staba
NORMAL HIGH-FREQUENCY OSCILLATORY NETWORK ACTIVITY
203
Spontaneous HFOs
·
Neocortical HFOs
· Neuronal
Correlates of HFOs in Normal Mammalian
Brain
·
Mechanisms Generating Normal HFOs
·
Physiological Role of HFOs
ABNORMAL HFOS IN EPILEPSY
205
Spatiotemporal
Properties of Pathological HFOs
·
Differences between Normal and Pathological
HFOs
·
HFOs in Patients with Epilepsy
·
Interietal Spikes and HFOs
·
Seizure Generation
and pHFOs
CONCLUSIONS
209
17.
INTERICTAL EPILEPTIFORM DISCHARGES IN PARTIAL EPILEPSY:
COMPLEX NEUROBIOLOGICAL MECHANISMS RASED ON
EXPERIMENTAL AND CLINICAL EVIDENCE
213
Marco
de
Curtis, John G.R Jefferys, and Massimo
Avoli
DIFFERENT
IED
PATTERNS IN EPILEPTIC PATIENTS. SPIKES
SPIKE BURSTS, SHARP WAVES
214
INTERICTAL SPIKES IN ACUTE AND CHRONIC ANIMAL
MODELS IN
VWO
215
IEDs IN ACUTE ANIMAL MODELS IN VITRO
215
HIGH-FREQUENCY OSCILLATIONS AS INTERICTAL EVENTS
217
THE SLOW COMPONENT AFTER THE INTERICTAL DISCHARGES
218
IN VITRO RECORDINGS OF IEDS FROM POSTSURGICAL
BRAIN TISSUE
220
CONCLUSIONS
223
Contents xvii
18. GABAA
RECEPTOR
FUNCTION IN TYPICAL ABSENCE SEIZURES
228
Vincenzo
Crunelli, Nathalie Leresche, and David W. Cope
TONIC GABAA INHIBITION
229
Enhanced Tonic GABAA Inhibition in Genetic Models of Typical Absence Seizures
·
GAT-1
Malfunction Underlies Increased Tonic GABAA Inhibition
·
Enhanced Tonic GABAA Inhibition
in the GHB Model: Role of GABABRs
·
Enhanced Tonic GABAA Inhibition of TC Neurons Is
Necessary and Sufficient for Typical Absence Seizure Generation
·
Significance of Tonic GABAA
Inhibition in Typical Absence Epilepsy
PHASIC GABAA INHIBITION
234
Phasic
GABA,
Inhibition in Cortex
·
Phasic GABAA Inhibition in TC Neurons
·
Phasic GABAA
А А А
Inhibition in NRT Neurons
ROLE FOR PHASIC AND TONIC GABAA INHIBITION IN THE GENESIS OF
ABSENCE SEIZURES
238
CONCLUDING REMARKS
238
19.
GABAg RECEPTOR AND ABSENCE EPILEPSY
242
Hua
A. Han, Miguel A. Cortez, and O. Carter Snead III
BACKGROUND ON
GABA,,
RECEPTORS
242
A Novel
GABA Receptor
·
Cloning and Characterization of the GABA|(R
·
Distribution of
GABAKR in the Central Nervous System
·
Developmental Profile of GABABRs in the CNS
PHYSIOLOGY OF THE GABA,,R
244
Intracellular Signal Transduction
·
Coupling of GABAHR to Ion Channels
TYPICAL VERSUS ATYPICAL ABSENCE SEIZURES
245
ANIMAL MODELS OF TYPICAL ABSENCE SEIZURES
246
Genetic Absence Epilepsy Rat from Strasbourg (GAERS)
·
WAG/Rij Rat
·
GHB-Treated
Rodent
·
Ih/lh Mouse
ANIMAL MODELS OF ATYPICAL ABSENCE SEIZURES
(AAS) 248
AY-9944-Treated
Rodents
·
Transgenic Mouse Models of Atypical Absence Seizures
GABAgR-MEDIATED MECHANISMS IN TYPICAL AND ATYPICAL
ABSENCE SEIZURES
249
TYPICAL AND ATYPICAL ABSENCE SEIZURES ARE CIRCUITRY DEPENDENT
250
IMPAIRMENT OF LEARNING AND MEMORY IN ATYPICAL
ABSENCE SEIZURES
251
GABABR Modulation of Learning and Memory
·
GABAgR-Mediated Mechanisms in Impairment
of Learning and Memory in Experimental Atypical Absence Seizures
CONCLUSION
252
20.
BRAINSTEM NETWORKS: RETICULOCORTICAL SYNCHRONIZATION
IN GENERALIZED CONVULSIVE SEIZURES
257
Čarí L. Faingold
AUDIOGENIC SEIZURES AS GENERALIZED CONVULSIVE
EPILEPSY MODELS
258
xviii Contents
NEURONAL NETWORK
FOR AGS
258
Inferior Colliculus
as the
AGS Initiation Site—
GABA
Mechanisms
·
Superior Colliculus in the AGS
Network · PAG in
the
AGS Network ·
Substantia
Nigra
in
the
AGS Network · BRF in
the AGS
Network ·
Changes in Nuclear Dominance during AGS
RETICULAR
FORMATION IN
CONVULSANT-INDUCED GENERALIZED
SEIZURE
INITIATION 261
RETICULAR
FORMATION
PLASTICITY—CONDITIONAL MULTIRECEPTIVE
NEURONS 262
SEIZURE REPETITION INDUCES
NEURONAL
NETWORK
CHANGES
263
Audiogenic Kindling in GEPR-Qs as a Model of Generalized Tonic-Clonic Seizures
· 1С
Changes in Audiogenic Kindling
·
Reticular
Formation
Neuronal
Firing Changes in
Audiogenic Kindling
·
Medial Geniculate Body Changes in Audiogenic Kindling
·
Amygdala
Changes in Audiogenic Kindling
·
Changes in the MGB-to-Amygdala Pathway in Audiogenic
Kindling
·
Molecular Mechanisms of Audiogenic Kindling in Amygdala
·
PAG Changes
in Audiogenic Kindling
·
Plasticity in the Amygdala-to-PAG Pathway in Audiogenic
Kindling
·
Cerebral Cortical
Neuronal
Firing in Audiogenic Kindling
·
Cerebral Cortex
Neuronal
Firing in Convulsant Drug-Induced Seizures
INTERACTIONS BETWEEN
NEURONAL
NETWORKS
266
Epilepsy Network-Respiratory Network Interaction
·
Pain Network-Epilepsy
Network Interaction
RETICULOCORTICAL SYNCHRONIZATION MECHANISMS
267
CONCLUSIONS
268
21.
ON THE BASIC MECHANISMS OF INFANTILE SPASMS
272
John W. Swann and Solomon L.
Moshe
INFANTILE SPASMS: THE CHALLENGES
272
INFANTILE SPASMS: THE QUESTIONS
277
INFANTILE SPASMS: THE OPPORTUNITIES
278
INFANTILE SPASMS: PROPOSED ANIMAL MODELS
279
The Conditional Deletion of the Aristaless-related-homeobox Gene (Arc) Mouse Model
·
The Triple Repeat Expansion Model of Arx
·
The NMDA Model
·
The Down
Syndrome-TsöSDn
Mouse Model
·
The CRH Hypothesis
·
The Multiple-Hit Model
·
The TTX Model of Focal
Neocortical Inactivation
CONCLUSIONS
283
22.
FAST OSCILLATIONS AND SYNCHRONIZATION EXAMINED WITH
IN VITRO MODELS OF EPILEPTOGENESIS
286
Roger D. Traub, Miles A. Whittington, and Mark O. Cunningham
DATA INDICATING THE EXISTENCE OF GAP JUNCTIONS BETWEEN
PRINCIPAL CORTICAL NEURONS
287
Contents xix
IN VITRO MODELS
OF VFO SUGGEST THAT
CHEMICAL
SYNAPSES ARE NOT
REQUIRED FOR THEIR
GENERATION 288
BRIEF VFO,
GENERATED BY NONSYNAPTIC MECHANISMS,
OCCURS DURING INTERICTAL BURSTS IN HUMAN EPILEPTOGENIC
TISSUE IN VITRO
288
EXAMPLE OF MORE SUSTAINED VFO PRIOR TO AN ELECTROGRAPHIC
SEIZURE IN A PATIENT S BRAIN IN SITU
291
VFO CAN BE ELICITED IN NEOCORTICAL SLICES IN NONSYNAPTIC
CONDITIONS ASSOCIATED WITH SPIKELETS IN DEEP PYRAMIDAL
NEURONS
291
SPATIAL PATTERNS OF VFO IN HUMAN EPILEPTIC BRAIN ARE
REPLICATED WITH A SIMPLE MODEL BASED ON LOCALIZED
ELECTRICAL COUPLING BETWEEN PYRAMIDAL NEURONS
294
DISCUSSION: CLINICAL IMPLICATIONS
295
23.
COMPUTER MODELING OF EPILEPSY
298
Marianne J. Case, Robert J. Morgan, Calvin J. Schneider, and Ivan
Soltész
COMPUTER MODELING TO PREVENT SEIZURES
300
Dynamic Therapies
·
Static Therapies
COMPUTER MODELING TO PREVENT EPILEPTOGENESIS
302
COMPUTER MODELING TO ASSIST RESEARCHERS
305
SUMMARY OF APPROACHES TO MODELING EPILEPSY
306
THE FUTURE OF COMPUTER MODELING OF EPILEPSY
307
COMPUTER MODELING RESOURCES
308
CONCLUSION
309
SECTION
3
MECHANISMS OF SEIZURES SUSCEPTIBILITY AND
EPILEPTOGENESIS
24.
TRAUMATIC BRAIN INJURY AND POSTTRAUMATIC EPILEPSY
315
David A. Prince, Isabel
Parada,
and Kevin D.
Graber
SPECTRUM OF POTENTIAL EPILEPTOGENIC MECHANISMS
INDUCED BY TBI
316
CHOICE OF MODELS FOR RESEARCH ON
PTE
317
PARTIAL NEOCORTICAL ISOLATION (UNDERCUT) MODEL
317
Abnormalities in Excitatory Mechanisms in Undercut Cortex
·
Abnormalities in GABAergic
Inhibitor) Mechanisms in Undercut Cortex
WHEN DOES POSTTRAUMATIC EPILEPTOGENESIS BEGIN?
321
xx Contents
PROPHYLAXIS OF POSTTRAUMATIC EPILEPTOGENESIS
322
Limiting Excitatory Connectivity
·
Preventing Structural/Functional Alterations
in GABAergic
Interneurons
IMPORTANT UNRESOLVED ISSUES AFFECTING APPLICATION OF
ANTIEPILEPTOGENIC THERAPIES FOR
PTE
324
25.
HEAD TRAUMA AND EPILEPSY
331
Asia
Pitkänen
and Tamuna Bolkvadze
POSTTRAUMATIC EPILEPSY IN HUMANS
331
EXPERIMENTAL MODELS OF
PTE
333
Epilepsy in the Fluid-Percussion Model
·
Epilepsy in the Controlled Cortical Impact Model
MOLECULAR AND CELLULAR REORGANIZATION DURING POSTTRAUMATIC
EPILEPTOGENESIS
336
SEARCH OF
BIOMARKERS
FOR POSTTRAUMATIC EPILEPTOGENESIS
338
PREVENTION OF EPILEPTOGENESIS AFTER TBI
338
SUMMARY
339
26.
FEVER,
FERRILE
SEIZURES, AND EPILEPTOGENESIS
343
Céline M. Dubé,
Shawn McClelland, ManKin Choy, Amy L. Brewster,
Ύοαυ
Noam, and Tallie Z.
Baram
INTRODUCTION
343
HOW DOES FEVER CAUSE SEIZURES?
344
Genetic Susceptibility to FS
·
Increased Brain Temperature as a Mechanism of FS
·
Fever
Mediators Lead to Seizures
·
Hyperthermia-Induced Hyperventilation and Alkalosis
DO FS CAUSE EPILEPSY?
345
WHICH FS CAUSE EPILEPSY?
345
HOW DO FS CAUSE EPILEPSY?
346
Inflammation and Cell Loss
·
Role of Changes in the Expression of Gene Sets, Including Ion
Channels, in FS-Induced Epileptogenesis
RELATIONSHIP BETWEEN FS,
MTS,
AND
TLE
348
FUTURE DIRECTIONS
348
27.
ROLE OF BLOOD-BRAIN BARRIER DYSFUNCTION IN EPILEPTOGENESIS
353
Alon Friedman and
Uwe Heinemann
BRAIN INSULTS AND INJURY TO THE BLOOD-BRAIN BARRIER
353
Mechanisms Underlying BBB Damage
BBB DYSFUNCTION FOLLOWING SEIZURES AND STATUS EPILEPTICUS
354
BBB DYSFUNCTION AND EPILEPTOGENSIS
355
The Role of Astrocytes in Epileptogenesis Induced by BBB Dysfunction
·
BBB Dysfunction and the
Role of
TGFß
Signaling in Epileptogenesis
Contents xxi
28.
CELL DEATH AND SURVIVAL MECHANISMS AFTER SINGLE AND
REPEATED BRIEF SEIZURES
362
David C.
Henshall
and Brian S. Meldrum
INTRODUCTION
362
Evidence from Animal Models that Single or Repeated Evoked Seizures Cause Neuron
Loss
·
Evidence Against Single and Repeated Evoked Seizures Causing Neuron Loss
·
Detection
of Acute Cell Death after Evoked Single and Repeated Brief Seizures
·
Do Spontaneous Seizures in
Epileptic Animals Cause Neuron Loss?
MOLECULAR MECHANISMS OF CELL DEATH FOLLOWING SINGLE AND
REPEATED BRIEF SEIZURES
364
Molecular Control of Apoptosis
·
Bel-2 Family Proteins
·
Evidence of Apoptosis-Assoeiated
Signaling Pathways after Brief Seizures
·
Summary: Animal Studies
HUMAN CLINICOPATHOLOGICAL STUDIES: IS THERE DAMAGE
PROGRESSION IN INTRACTABLE
TLE?
368
Hippocampal Neuron Loss in Human
TLE
·
Pathology in Nonhippocampal
Regions
·
Neuroimaging Evidence of Damage Progression in Intractable
TLE
·
Summary: Imaging
Evidence of Seizure-Induced Neuron Loss in Human Studies
·
Histological Evidence of Acute Cell
Death in Human
TLE
MOLECULAR EVIDENCE OF APOPTOSIS-ASSOCIATED SIGNALING IN
HUMAN
TLE
370
Bel-2 and Caspase Family
Cienes
·
Findings from Other Cohorts
·
Other Caspuscs
·
Other Pro- and Anti-Apoptotie Proteins
·
Summary: Molecular Evidence of Apoptosis
in Human
TLE
M
ITOCI lONDRIAL
DNA
DAMAGE IN EPILEPSY
372
CHAPTER SUMMARY AND FUTURE QUESTIONS
372
29.
PROGRAMMED NECROSIS AFTER STATUS EPILEPTICUS
377
Jerome Niquet, Maria-Leonor Lopez-Meraz, and Claude G. Wasterlain
INTRODUCTION
377
SEIZURE-INDUCED
NEURONAL
INJURY
378
Neuronal
Injury and
SE
·
Is Seizure-Associated
Neuronal
Injury Due to the Seizures Themselves or
to Seizure-Associated Systemic Factors?
NECROSIS AND APOPTOSIS IN EXPERIMENTAL MODELS
OF EPILEPSY
379
Necrosis and Apoptosis: A Morphological Definition
·
Following
SE,
Necrosis Is the Main Form
of
Neuronal
Death in the Adult Brain
... · ...
And in the Developing Brain, Too
·
Mechanisms of
Seizure-Induced
Neuronal
Necrosis
30.
HISTOPATHOLOGY OF HUMAN EPILEPSY
387
Nihal
С
de
Lanerolle, Tih-Shih Lee, and Dennis D. Spencer
INTRODUCTION
387
HISTOPATHOLOGICAL VARIATIONS IN
TLE
HIPPOCAMPUS
389
xxii Contents
REORGANIZATION OF THE DENTATE GYRUS IN SCLEROTIC
HIPPOCAMPUS
390
Neuronal
Changes in Dentate Gyms
·
Plasticity of
Neuronal
Fibers
·
Changes in
Neurotransmitter
Receptors
·
Implications of Reorganizational Changes in the Dentate Gyrus
CHANGES IN AMMON S HORN AND THE ROLE OF ASTROCYTES
393
Neurons
·
Astrocytes
·
Astrocytes and the Microvasculature
·
Astrocyte Types
·
Probable Roles
of Astrocytes in a Seizure Focus
GENE EXPRESSION IN SEIZURE FOCUS
396
SURICULUM
397
ENTORHINAL CORTEX
397
PROBABLE PATHOPHYSIOLOGICAL MECHANISMS OF SEIZURE
GENERATION
398
SPECULATION ON FUTURE CHALLENGES IN THE AREA
398
IMPACT ON FINDING CURES AND REPAIRS FOR EPILEPSIES
399
31.
THE TIME COURSE AND CIRCUIT MECHANISMS OF ACQUIRED
EPILEPTOGENESIS
405
E
Edward
Dudek
and Kevin
].
Staley
TWO MODELS OF ACQUIRED EPILEPSY
406
THE TIME COURSE OF ACQUIRED EPILEPTOGENESIS
406
The Progressive Nature of Acquired Epilepsy
·
The Latent Period and the Duration
of Epileptogenesis
CIRCUIT MECHANISMS AND SYNAPTIC REORGANIZATION
408
Synaptic Reorganization
·
Loss of GABAergic
Interneurons
·
Axon Sprouting and Increased
Recurrent Excitation
POSSIBLE CONCLUSIONS
412
32.
MOSSY FIBER SPROUTING IN THE DENTATE GYRUS
416
Paul S. Buckmaster
UNDER WHAT CIRCUMSTANCES DOES MOSSY FIBER SPROUTING
OCCUR?
416
HOW DOES MOSSY FIBER SPROUTING DEVELOP?
417
WHAT ARE THE FUNCTIONAL CONSEQUENCES OF MOSSY FIBER
SPROUTING?
421
33.
KAINATE AND TEMPORAL LOBE EPILEPSIES: THREE DECADES
OF PROGRESS
432
Yehezkel Ben-Ari
INTRODUCTION
432
Contents xxiii
SEIZURES AND BRAIN DAMAGE PRODUCED BY KAINATE IN THE
ADULT BRAIN
434
The Kainate Model of
TLE
·
Seizure-Specific and Nonspecific Cell Loss Produced by
Kainate
·
Loss of GABAergic
Interneurons
and Failure of Inhibition
·
Physiological Actions
of Kainate on Hippocampal Neurons
·
The Yin and the Yang of Kainate Receptors: Molecular
Considerations
SEIZURES BUT NO BRAIN DAMAGE PRODUCED BY KAINATE IN PUPS
438
Maturation of the Kainate System
·
Recurrent Seizures in the Immature Brain Produce
Long-Term
Effects
ROLE OF KAINATERGIC SYNAPSES IN SEIZURE-INDUCED
EPILEPTOGENESIS
440
The Mossy Fibers: An Ideal Location to Look for Changes
·
Mossy Fibers Have an Intimate Relation
with Kainate Signaling
·
Mossy Fibers Sprout after Seizures: Anatomical Observations
·
Recurrent
Mossy Fiber Synapses in
TLE
Include Kainatergic Synapses that Are Not Observed in Naive
Neurons
·
Implications of Kainatergic Pathways for the Development of Efficient Antiepileptic Agents
SEIZURES BEGET SEIZURES IN VITRO IN THE DEVELOPING HIPPOCAMPUS
444
An Experimental Protocol to Generate an Epileptogenic Mirror Focus
·
Conditions Required for
Recurrent Seizures to Generate a Mirror Focus
GENERAL CONCLUSIONS
446
34.
ABNORMAL DENTATE GYRUS NETWORK CIRCUITRY IN TEMPORAL
LOBE EPILEPSY
454
Robert S. Sloviter, Argyle V.
Витапціац,,
Robert Sehwarcz, and Michael Frotscher
DEFINING EPILEPTOGENESIS
454
WHY FOCUS ON TEMPORAL LOBE EPILEPSY AND THE DENTATE
GYRUS?
455
EPILEPTOGENIC NEURON LOSS AND IMMEDIATE GRANULE CELL
HYPEREXCITABILITY: IS NEURON LOSS SUFFICIENT TO CAUSE EPILEPSY?
455
Redefining the Term Epileptogenesis
·
HyperexcitabL· Is Not Synonymous with Spontaneously
Epileptic: Does Hippocampal Epileptogenesis Require a Second Pathology?
MOSSY FIBER SPROUTING
459
Inhibitory Circuitry, Mossy Cells, and Mossy Fiber Sprouting
·
Must Mossy Fiber Sprouting Be
Either Entirely Excitatory or Entirely Inhibitory?
GRANULE CELL DISPERSION
462
THE LATENT PERIOD AND EPILEPTOGENESIS
463
A GRID CELL HYPOTHESIS OF TEMPORAL LOBE EPILEPTOGENESIS
464
CONCLUSION
465
35.
ALTERATIONS IN SYNAPTIC FUNCTION IN EPILEPSY
470
Christophe
Bernard
PRESYNAPTIC MODIFICATIONS
471
Cell Death
·
Neosynaptogenesis
·
Presynaptic Terminal
xxiv Contents
POSTSYNAPTIC
MODIFICATIONS
475
Trafficking of GAB
Ад
Receptors in Epilepsy
·
Changes in Subunit Composition
·
Alterations in
Chloride Homeostasis
GLIAL MODIFICATIONS
478
FUNCTIONAL CONSEQUENCES OF THESE MODIFICATIONS
479
Interictal Activity
·
Cognitive Deficits
REPAIR STRATEGIES
480
CONCLUSION
480
36.
SEIZURE-INDUCED FORMATION OF BASAL
DENDRITES
ON GRANULE
CELLS OF THE RODENT DENTATE GYRUS
484
Charles E. Ribak, Lee A. Shapiro, Xiao-Xin Yan, Khashayar Dashtipour, J. Victor Nadler,
Andre Obenaus, Igor Spigelman, and Paul S. Buckmaster
SEIZURE-INDUCED
HILAR
BASAL
DENDRITES
IN RODENTS
485
SYNAPTIC CONNECTIONS OF
HILAR
BASAL
DENDRITES
486
Excitatory Synapses
·
Inhibitory Synapses
TIME COURSE FOR BASAL
DENDRITE
FORMATION FOLLOWING
SEIZURE ACTIVITY
488
DO BASAL
DENDRITES
ARISE FROM NEWLY GENERATED
NEURONS?
489
WHAT GUIDES THE BASAL
DENDRITES
TO GROW INTO
THE
HILUS?
490
37.
PERTURBATIONS OF DENDRITIC EXCITABILITY IN EPILEPSY
494
Cha-Min Tang and Scott M. Thompson
A BRIEF HISTORY OF THE ACTIVE
DENDRITE
494
ELECTRICAL COMPARTMENTALIZATION OF
DENDRITES:
THE INTERSECTION OF FORM AND FUNCTION
495
THE TERMINAL
DENDRITE
AS AN ELECTRICAL
COMPARTMENT
496
Perturbations Affecting the Thin Distal Electrical Compartment
·
Attenuation of
Ід
Lowers the Threshold for Regenerative Spiking
·
Downregulation of Ih Increases Input
Impedance
·
Downregulation of SK Channels Leads to Prolonged Spikes in Terminal
Dendrites
THE APICAL TRUNK AS AN INDEPENDENT ELECTRICAL
COMPARTMENT
500
Perturbations of the Apical Trunk Compartment
COUPLING BETWEEN DIFFERENT DENDRITIC COMPARTMENTS
502
Perturbations of Coupling between the
Soma
and the Apical Tuft
THE EPILEPTIC NEURON VERSUS THE EPILEPTIC NETWORK
503
Contents xxv
38. NEUROGENESIS
AND EPILEPSY
506
Jack
M.
Parent and Michelle M. Kron
ADULT NEUROGENESIS IN THE EPILEPTIC BRAIN
506
MORPHOLOGICAL ABNORMALITIES IN MTLE: ROLE OF
NEUROGENESIS
507
Mossy Fiber Sprouting
·
Hilar
Ectopie
Granule Cells
·
Hilar
Basal
Dendrites
FUNCTIONAL IMPLICATIONS OF DGC ABNORMALITIES IN MTLE
509
Mossy Fiber Sprouting
·
HBDs and
Hilar
Ectopie
Granule Cells
COMORBIDITIES ASSOCIATED WITH MTLE
510
39.
TEMPORAL LOBE EPILEPSY AND THE BDNF RECEPTOR, TrkB
514
James O. McNamara and Helen E. Scharfman
INTRODUCTION
514
MTLE: A PROGRESSIVE DISORDER IN HUMANS AND
ANIMAL MODELS
515
SEIZURES: A PATHOLOGICAL FORM OF
NEURONAL
ACTIVITY
515
BDNF: AN ATTRACTIVE CANDIDATE GENE
516
EVIDENCE IMPLICATING BDNF AND TrkB IN MTLE
516
Animal
Models In Vivo
·
Limbie
Seizures Enhance TrkB Activation
·
Potential Cellular
Consequences of TrkB Activation Induced In Seizures
WHAT IS THE MOLECULAR MECHANISM MEDIATING TrkB ACTIVATION
BY SEIZURES IN VIVO?
518
THE POTENTIAL ROLE OF BDNF IN CATAMENIAL EPILEPSY
519
CATAMENIAL EPILEPSY: DEFINITION AND POTENTIAL MECHANISMS
521
ALTERNATIVE EXPLANATIONS FOR CATAMENIAL EPILEPSY BASED ON THE
INTERPLAY BETWEEN ESTROGEN, PROGESTERONE, AND BDNF
521
The Role of BDNF in the Actions of Estrogen
·
The Role of BDNF in the Actions of Progesterone
SUMMARY
526
CONCLUDING REMARKS
526
40.
ALTERATIONS IN THE DISTRIBUTION OF GABAA RECEPTORS
IN EPILEPSY
532
Carolyn R.
Houser,
Nianhui Zhang, and Zechun Peng
MULTIPLE CHANGES IN GABAAR SUBUNITS IN EPILEPSY
532
FRAMEWORK FOR VIEWING GABAAR SUBUNIT CHANGES IN EPILEPSY
533
DECREASED EXPRESSION OF GABAAR SUBUNITS IN PRINCIPAL CELLS
533
Decreased
0(5
Subunit
Expression
·
Decreased
б
Subunit Expression
·
Decreased
αϊ
Subunit
Expression
·
Functional Consequences of Decreased a5 and
б
Subunit Expression in
Principal Cells
xxvi Contents
INCREASED
EXPRESSION
OF
GABA^R
SUBUNITS IN
PRINCIPAL
CELLS
536
Functional Consequences of Increased GABA^R
Subunit
Expression in Principal Cells: Potential
Alterations in
Subunit
Composition
·
Other Proposed Effects of Altered GABAAR
Subunit
Composition
ALTERED GABAAR SUBUNIT EXPRESSION IN
INTERNEURONS
540
SUMMARY
541
Emerging Views and Questions
·
Future Prospects and Challenges
41.
GABAA RECEPTOR PLASTICITY DURING STATUS EPILEPTICUS
545
Suchitra Joshi and Jaideep Kapur
ANIMAL MODELS OF
SE
546
REDUCED GABAERGIC
NEUROTRANSMISSION
DURING
SE
547
GABARS 547
GABAR-MEDIATED INHIBITION IS DECREASED DURING
SE
547
INCREASED INTERNALIZATION OF SYNAPTIC
GABARS
DURING
SE
548
SE-INDUCED DEPHOSPHORYLATION OF
GABARS
DECREASES THEIR CELL
SURFACE STABILITY
549
DECREASED BENZODIAZEPINE SENSITIVITY WITH SEIZURE PROGRESSION
IN ANIMAL MODELS OF
SE
549
TONIC INHIBITION MEDIATED BY
GABARS
DURING
SE
550
GABAR
FUNCTION IN CATAMENIAL EPILEPSY
550
CONCLUSIONS
551
42.
PLASTICITY OF GABAA RECEPTORS RELEVANT TO NEUROSTEROID
ACTIONS
555
István
Mody
GABA.RS RESPONSIBLE FOR TONIC INHIBITION
555
Λ
ALTERED TONICALLY ACTIVE
GABA RS
IN THE DENTATE GYRUS IN AN
ANIMAL MODEL OF
TLE
557
POSSIBLE CONSEQUENCES OF ALTERED NEUROSTEROID PHARMACOLOGY
IN THE DENTATE GYRUS AFTER
TLE
558
43.
GABA
RECEPTOR PLASTICITY IN ALCOHOL WITHDRAWAL
562
Richard W.
Olsen
and Igor Spigelman
INTRODUCTION
562
RESULTS
563
The
CIE
Model and Its Relationship to Human Alcoholism
Contents xxvii
DISCUSSION
566
The
CIE
Model of Alcoholism and
GABAR
·
Other Studies on Chronic EtOH and Other
Drag-Induced
GABAR
Plasticity
·
GABAR
Plasticity in Epilepsy
44.
REGULATION OF GABAA RECEPTOR GENE EXPRESSION
AND EPILEPSY
574
Amy R. Brooks-Kay
al
and Shelley J. Russek
ROLE OF GABAA RECEPTORS IN EPILEPSY
574
MECHANISMS REGULATING GABAA RECEPTOR
SUBUNIT EXPRESSION
575
al Subunit
Regulation
·
0í4
Subunit
Regulation
CONCLUSION
578
45.
CHLORIDE HOMEOSTASIS AND
GABA
SIGNALING IN TEMPORAL
LOBE EPILEPSY
581
Richard Miles, Peter Blaesse,
Gilles
Huberfeld, Lucia
Wittner,
and
Kai Kaila
HUMAN INTERICTAL ACTIVITY AND
CL
HOMEOSTASIS
581
GABA
AND CL- REGULATION SYSTEMS
583
Changes in Ch-Regulating Systems in Pathological States
CL HOMEOSTASIS AND ICTAL ACTIVITIES
585
CL REGULATION AND EPILEPTIFORM ACTIVITIES IN THE YOUNG
586
MOLECULES REGULATING CL HOMEOSTASIS AS TARGETS FOR
ANTI-EPILEPTIC DRUGS
586
46.
ASTROCYTES AND EPILEPSY
591
Jerome Clasadonte and Philip G. Haydon
CA2+ SIGNALS IN ASTROCYTES
592
In Vitro and In Situ Studies
·
In Vivo Studies
ASTROCYTES RELEASE CHEMICAL TRANSMITTERS TO MODULATE
NEURONAL
AND SYNAPTIC FUNCTIONS
594
Release of
Glutamate
·
Release of D-Serine
·
Release of ATP
·
Adenosine Derived from
Astrocyte-Released ATP
REACTIVE ASTROCYTOSIS AND EPILEPSY
597
Reactive Astrocytosis and GS Downregulation in Epilepsy
·
Reactive Astrocytosis and ADK
Upregulation in Epilepsy
ASTROCYTIC CA2+ SIGNALS,
GLUTAMATE
RELEASE, AND EPILEPSY
599
Astrocytic Ca2+ Signals and Epilepsy
·
Astrocytic
Glutamate
Release and Epilepsy
CONCLUDING REMARKS
601
xxviii Contents
47.
ASTROCYTE DYSFUNCTION IN EPILEPSY
606
Christian
Steinhäuser
and Gerald
Seifert
IMPAIRED K+ BUFFERING IN TEMPORAL LOBE EPILEPSY
607
Loss of Inwardly Rectifying K+ Channels in MTLE
·
Gap Junctions and K+ Buffering
·
Interplay
between Kir Channels and AQP4 in K+ Buffering
AMBIGUOUS ROLE OF GAP JUNCTIONS IN EPILEPTOGENESIS
610
GLUTAMATE
UPTAKE IN EPILEPSY
611
Glutamate
Transporter in Astrocytes
·
Conversion of
Glutamate
to
Glutaminę
by Astrocytes
CONCLUDING REMARKS
613
48.
GLIA-NEURON INTERACTIONS IN ICTOGENESIS AND EPILEPTOGENESIS:
ROLE OF INFLAMMATORY MEDIATORS
618
Annamária Vezzani,
Stephan Auvin,
Teresa Ravizza, and
Eleonora Aronica
CLINICAL FINDINGS
619
Inflammatory and Immunological
Biomarkers
·
Genetic Studies
·
Anti-inflammatory Drugs in
Epilepsy
·
Infectious and Autoimmune Diseases
·
Focal Epilepsy (Noninfectious, Nonautoimmune)
FOCAL MALFORMATIONS OF CORTICAL DEVELOPMENT
622
Tuberous Sclerosis Complex
·
Focal Cortical Dysplasias
·
Glioneuronal Tumors
EXPERIMENTAL MODELS
624
Models of Seizures in Adult Animals
Models of Seizures in Immature Animals
·
Inflammation
and Seizure-Induced Cell Injury in Immature Brain
·
Long-Term
Consequences of Inflammation for
Immature Brain
·
Mechanisms of Hyperexcitability
CONCLUSIONS
629
49.
GLIA-NEURON INTERACTIONS
635
Giuseppe Biagini,
Carla Mannelli,
Gabriella
Panuccio,
Giulia
Puia,
and Massimo
Avoli
BACKGROUND
635
MULTIFACETED GLIAL MODULATION OF
NEURONAL
EXCITABILITY
637
Astrocyte-Neuron Interactions Leading to Synchronization in Undamaged Tissue
·
Astrocyte-Neuron
Interactions Leading to Synchronization in Damaged Tissue
·
Microglia—Neuron Interactions
NEUROSTEROIDS AND EPILEPTOGENESIS
639
P450SCC and Epileptogenesis
·
öa-Reduced
Neurosteroids and Epileptogenesis
·
Neurosteroids,
Epileptogenesis, and Inhibition
CONCLUSIONS
644
SECTION
4
EPILEPSY GENES AND DEVELOPMENT
50.
GENETIC EPIDEMIOLOGY AND GENE DISCOVERY IN EPILEPSY
651
Ruth Ottman and and Neil Risch
EPILEPSY AS A COMPLEX DISEASE
651
Complexities in Phenotype Definition: Lessons from Mendelian Epilepsies
Contents xxix
GENE IDENTIFICATION IN
THE COMPLEX
EPILEPSIES
653
Positional Cloning
·
Allelic Association Studies
·
Massively Parallel Sequencing
PHENOTYPE DEFINITION
657
Familial Aggregation Studies
·
Family Concordance Studies
RECOMMENDATIONS FOR FUTURE STUDIES
658
51.
STRATEGIES FOR STUDYING THE EPILEPSY GENOME
663
Thomas
N.
Ferravo,
Dennis
J.
Dlugos,
Hakon
Hakonarson, and Russell
J
.
Buono
THE EPILEPSY GENOME
663
MODELING COMMON FORMS OF EPILEPSY FOR GENOMIC STUDIES
664
Phenotypic Models
·
Hypothetical Genetic Models
NEW RESEARCH APPROACHES TO THE EPILEPSY GENOME
666
Genetic Association
·
Next-Generation Sequencing
CONCLUDING REMARKS
670
52.
SODIUM CHANNEL MUTATIONS AND EPILEPSY
675
William A. Catterall
INTRODUCTION
675
VOLTAGE-GATED SODIUM CHANNELS
675
SODIUM CHANNEL MUTATIONS IN GENERALIZED EPILEPSY WITH FEBRILE
SEIZURES PLUS
676
Effects of GEFS+ Mutations Expressed in
Nonneuronal
Cells
·
Defective Protein Folding and
Partial Rescue of GEFS+ Mutants
·
GEFS+ Mutations in Mouse Genetic Models
SEVERE MYOCLONIC EPILEPSY OF INFANCY
678
Loss of Excitability of GABAergic
Interneurons
and Hyperexcitability in SMEI
·
Selective Deletion
of Na^.l
· 1
Channels in Inhibitory Neurons
·
Loss of Excitability of GABAergic
Interneurons
and
Comorbidities in SMEI
·
Thermally Induced Seizures in a Mouse Model of SMEI
·
Balancing
Excitation and Inhibition with Genetic Compensation and Drug Treatment
POTENTIAL ROLE OF MUTATIONS IN NAyl.l CHANNELS IN FEBRILE
SEIZURES IN CHILDHOOD
682
A UNIFIED LOSS-OF-FUNCTION HYPOTHESIS FOR N^l.l GENETIC
EPILEPSIES
682
MUTATIONS OF OTHER N CHANNELS IN EPILEPSY
683
53.
POTASSIUM CHANNELOPATHIES OF EPILEPSY
688
Robert Brenner and Karen S. Wilcox
INTRODUCTION
688
WHAT ARE POTASSIUM CHANNELS?
688
KCNA1
·
Effect of KCNA1 Epilepsy Mutations on Potassium Currents
·
KCNA1 and
Sudden Unexplained Death in Epilepsy
·
KCNA1 Channelopathy as a Consequence of
xxx Contents
LGIl
Mutations
· KCND2 · KCND2 Channelopathy Mutation ·
Acquired Changes in
KCND2
and Seizures
· KCNMA1 · KCNMA1
Gating Properties
·
BK
Channel
Function
in Neurons ·
BK
Channels
and Acquired Epilepsy
· Human
BK
Channel
Epilepsy
Channelopathy · KCNQ Channelopathy
Mutations
· KCNQ
Mutations and Animal
Models · KCNQ1 · KCNJ10 · KCNJU
CONCLUSIONS
697
54.
THE VOLTAGE-GATED CALCIUM
CHANNEL AND
ABSENCE EPILEPSY
702
Jeffrey
L. Noebels
TOTTERING, ITS EPILEPTOGENIC ALLELES, AND INTERACTING
SUBUNITS 703
HOW LOSS-OF-FUNCTION CACNA1A MUTATIONS IMPAIR
NEURONAL
NETWORKS 704
Somatodendriüc
Compartment
· Axon Initial Segment · Presynaptic Terminal and Exocytosis
CALCIUM
CHANNEL
REGULATORY SUBUNIT RESHUFFLING AND
EMERGENT SPIKE-WAVE
NETWORKS 705
DYSAFFERENTATION
AS A CONVERGENT PATHWAY TO ABSENCE EPILEPSY
IN DEVELOPING BRAIN
706
RESCULPTING THALAMIC EXCITABILITY: INVOLVEMENT OF T-TYPE
CURRENTS
707
Evaluating the
Т
-Type
Contribution
·
Other P/Q Channel- Induced Downstream Plasticity
TRANSLATIONAL ADVANCES TOWARD THE TREATMENT OF INHERITED
CALCIUM CHANNEL EPILEPSIES
708
When Does
Cacnö-Zd-Mediated Pathogenesis
Begin?
EPISTATIC INTERACTIONS
709
SUMMARY
710
55.
MUTATED GABAA RECEPTOR SUBUNITS IN IDIOPATHIC
GENERALIZED EPILEPSY
714
Patrick Cossette, Pamela Lachance-Touchette, and Guy A. Rouleau
INTRODUCTION AND HISTORICAL PERSPECTIVES
714
DEFINITION AND CLASSIFICATION
715
GENETIC EVIDENCE FOR IDIOPATHIC EPILEPSIES
715
Familial Aggregation Studies
·
Twin Studies
·
Complex Inheritance Patterns in Idiopathic Epilepsy
FAMILIAL FORMS OF IDIOPATHIC EPILEPSIES
716
Molecular Mechanisms Underlying Familial Epilepsies
·
Rare Syndromes Caused by Mutations
in Complementary Subunits
·
Autosomal Dominant Forms of Classical Idiopathic Generalized
Epilepsy
STRUCTURE AND FUNCTION OF GABAA RECEPTORS
718
Distribution and Structural Diversity of the GABAA Receptors
·
Genomic Evolution of GAB AA
Receptor Genes in Homo sapiens
·
Functional Properties of the GAB
Ад
Receptors
Contents xxxi
IMPAIRED FUNCTION OF MUTATED GABAA RECEPTORS
720
Clinical Manifestations Associated with Mutations in GABAA Receptor Subunits
·
Mutations in
GABAA Receptor Subunits Generally Produce Loss of Function
·
The Complex Case of GABRD
Mutations
·
Animal Models with Mutations in GABAA Receptor Subunits
MUTATIONS IN VOLTAGE-GATED CHLORIDE CHANNELS
724
GABA
PERFORMS CRITICAL FUNCTIONS IN THE DEVELOPING BRAIN
724
FUTURE PERSPECTIVES
725
56.
THE GABAAy2(R43Q) MOUSE MODEL OF HUMAN GENETIC EPILEPSY
731
Steven
Petrou
and Christopher A. Reid
UTILITY OF MOUSE MODELS IN UNDERSTANDING PATHOGENESIS IN
EPILEPSY
731
THE GABAA RECEPTOR
731
GABAj2 RECEPTORS AND GENETIC EPILEPSY
732
GABAj2(R43Q) FUNCTIONAL ANALYSIS IN HETEROLOGOUS EXPRESSION
SYSTEMS
732
THE GABAj2(R43Q) MOUSE MODEL
732
Cortical Inhibition as a Common Deficit in R43Q Patients and Mice?
·
Febrile Seizures in
R43Q Patients and Mice
·
Developmental Role of the R43Q Mutation
·
R43Q as a Model for
Ilypoglyceinia-Iiidiieed
Seizures
FUTURE CHALLENGES
737
57.
GABAA RECEPTOR SUBUNIT MUTATIONS AND GENETIC EPILEPSIES
740
Robert L.
Macdonald,
Jing-Qiong Kang, and Martin J. Gallagher
INTRODUCTION
740
GABAA RECEPTOR SUBUNIT GENES
741
IES
ASSOCIATED WITH GABAA RECEPTOR SUBUNIT MUTATIONS
743
PATHOPHYSIOLOGY OF GABAA RECEPTOR SUBUNIT MUTATIONS ASSOCIATED
WITH
CAE
AND
JME
743
Ѕ,
S15F, G32R)
·
GABRAl(975delC, S326fs328X)
·
GABKAi(A322D)
PATHOPHYSIOLOGY OF GABAA RECEPTOR SUBUNIT MUTATIONS ASSOCIATED
WITH FS WITH OR WITHOUT
CAE
744
GABRG2(R82Q)
·
GABHG2(R177G)
·
GABRG2(WS6
+
2Т-Ю)
PATHOPHYSIOLOGY OF GABAA RECEPTOR SUBUNIT MUTATIONS ASSOCIATED
WITH GEFS+ AND DRAVET SYNDROME
745
GAB«G2(K328M)
·
GAB«G2(Q390X)
·
GABRG2(Q40X and Q429X)
·
GABRDi
E
1
77A, R220H,
andR220C)
DISCUSSION
746
Phenotype-Genotype Correlations
·
Expression of GABAA Receptor Subunit Mutations in Heterologous
Cells and Neurons
·
Pathophysiological Mechanisms of GABAA Receptor Subunit Mutations
xxxii Contents
58. NICOTINIC ACETYLCHOLINE
RECEPTOR
MUTATIONS
750
Ortrud
К.
Steinlein, Sunao Kaneko, and Shinichi Hirose
INTRODUCTION
750
CLINICAL SPECTRUM OF ADNFLE
751
EEG
AND BRAIN IMAGING IN ADNFLE PATIENTS
752
A Case
ADNFLE MUTATIONS IN nACHR SUBUNITS
753
NEURONAL
nACHRs
753
IN VITRO EXPRESSION OF ADNFLE MUTATIONS
754
ORIGIN OF SEIZURES
755
GENOTYPE-PHENOTYPE CORRELATIONS IN ADNFLE
755
ANIMAL MODELS OF ADNFLE: WHAT DID WE LEARN?
756
Specific Criteria for Genetic Animal Models of ADNFLE
·
Validity of Genetic Animal Models
of ADNFLE
·
Pathophysiology of ADNFLE
KEY QUESTION: WHY DO nACHR MUTATIONS CAUSE
EPILEPSY?
758
CONCLUSIONS
759
59.
GENE INTERACTIONS AND MODIFIERS IN EPILEPSY
763
Miriam H. Meisler and
Janelle
E.
O Brien
INTRODUCTION
763
WITHIN-FAMILY HETEROGENEITY MAY REFLECT THE SEGREGATION
OF GENETIC MODIFIERS
764
Variability in Families with GEFS+
·
Mildly Affected Carriers in a Family with Dravet
Syndrome
·
Parental Mosaicism in One-Generation Families with Multiplex
Dravet Syndrome
LINKAGE EVIDENCE FOR DIGENIC INTERACTION IN
HUMAN EPILEPSY
765
Digenic Inheritance of Febrile Seizures with Temporal Lobe Epilepsy
·
Digenic Inheritance
of Epilepsy in Families with Light Sensitivity and Myoclonic Epilepsy
INTERACTING ION CHANNEL MUTATIONS IN
MOUSE MODELS
766
Mouse Scn2a and Kcnq2
·
Interaction between Mouse Scnla and Scn8a
·
Mouse Calcium
Channel Cacnala and Potassium Channel Kcnal
·
Human SCN9A as a Potential Modifier of Dravet
Syndrome
INBRED STRAINS OF MICE PROVIDE ACCESS TO ADDITIONAL MODIFIERS
OF EPILEPSY GENES
767
Mouse Modifier Genes and Human Epilepsy
·
Genetics of Complex Epilepsy
FUTURE PROSPECTS FOR UNDERSTANDING GENE INTERACTION
IN HUMAN EPILEPSY
769
Contents xxxiii
60.
RARE GENETIC CAUSES OF LISSENCEPHALY MAY IMPLICATE
MICROTUBULE-BASED TRANSPORT IN THE PATHOGENESIS
OF CORTICAL DYSPLASIAS
771
Judy S. Liu, Christian R. Schubert, and Christopher A. Walsh
INTRODUCTION
771
IMPLICATIONS OF MICROTUBULE ASSEMBLY AND MICROTUBULE-BASED
TRANSPORT FOR
NEURONAL
DEVELOPMENT
773
LISI
IS THE CAUSATIVE GENE ASSOCIATED WITH MILLER-DIEKER
LISSENCEPHALY SYNDROME
778
DCX
MUTATIONS CAUSE BOTH
Х
-LINKED LISSENCEPHALY AND
SUBCORTICAL
BAND HETEROTOPIA
779
MUTATIONS IN a-TUBULIN CAUSE LISSENCEPHALY
780
MICROTUBULE FUNCTION AND THE PATHOGENESIS OF SEIZURES
781
CORTICAL MALFORMATIONS ARE AN IMPORTANT CAUSE
OF
PEDIATRIC
EPILEPSY
781
61.
THE GENERATION OF CORTICAL
INTERNEURONS
786
Diego M. Qelman, Oscar
Marín,
and
Jolin
L.R. Rubenstein
INTRODUCTION
786
THE MEDIAL GAXCLIOXJC EMIXENCE GENERATES THE MAJORITY
OF CORTICAL
INTERNEURONS 7S7
THE CAUDAL GAXGLIOXIC EMINENCE PRODUCES DISTINCT
INTERNEURON
SUBTYPES
790
THE PREOPTIC AREA GENERATES SEVERAL CLASSES OF CORTICAL
INTERNEURONS
792
OVERVIEW
793
62.
GENES IN INFANTILE EPILEPTIC ENCEPHALOPATHIES
797
Christel
Depienne,
Isabelle Gourfinkel-An, Stéphanie
Baulac, and Eric LeGuern
INTRODUCTION
797
THE MONOGENIC FORMS OF EIEES
798
Dominant Mutations Responsible for EIEE Mostly Occur
de Novo
·
GCÍ/SLC25A22,
a Gene
Responsible for Rare Autosomal Recessive
(AR) EIEE
with a Suppression-Rurst Pattern
·
X-Iinked EEs
A GENETICALLY DETERMINED INFANTILE
ЕЕ.
DRAVET SYNDROME
(OR SEVERE MYOCLONIC EPILEPSY OF INFANCY)
803
Clinical Context
·
De Novo
Mutations in
ЅСЅЧА
Are the Main Cause of DS
·
DS-Like Syndrome
in Females Associated with Mutations in the PCDH19 Gene
PROSPECTS AND CONCLUSION
806
Identification of a Mutation Leads to Genetic Counseling
·
Recent Strategies to Identify New
Cienes
Responsible for EEs
xxxiv Contents
63.
DEVELOPING
MODELS
OF
ARISTALESS-RELATED HOMEOBOX
MUTATIONS
813
Eric
D. Marsh
and Jeffrey A. Golden
INTRODUCTION
813
ARX
IN CLINICAL NEUROLOGY
814
MOLECULAR
BIOLOGY OF ARX
815
What Is ARX?
·
Ane
as a Transcriptional
Repressor
·
Role in
Interneuron
Development
·
Role in
Cortical VZ Development
·
Role of Expansion Mutations
ARX MODELS
818
ARX as Disease Mediator
FUTURE DIRECTIONS IN THE STUDY OF ARX
820
64.
HAPLOINSUFFICIENCY OF STKBP1 AND OHTAHARA
SYNDROME
824
Hirotomo Saitsu, Mitsuhiro
Kato,
and Naomichi Matsumoto
INTRODUCTION
824
OHTAHARA SYNDROME
824
DE NOVO STXRPl
MUTATIONS CAUSE OS
825
Identification of STXBP1 Mutations in Patients with OS
·
STXBP1 Mutation Is a Major Genetic
Cause of OS
·
Clinical Features of Patients with STXBP1 Deletion/Mutations
MOLECULAR EVIDENCE OF STXBP1 HAPLOINSUFFICIENCY
829
Mutant STXBP1 Proteins Are Unstable
·
Degradation of Mutant STXBP1 Proteins
·
Degradation
of STXBP1 mRNA with Abnormal Splicing
HOW WOULD HAPLOINSUFFICIENCY OF STXBP1
LEAD TO OS?
831
Impairment of Synaptic Vesicle Release
·
Possible Interneuropathy
·
Cell Death
of the Brainstem
FUTURE CHALLENGES
832
Expansion of the Clinical Spectrum of STXBP1 Mutations
·
Animal Model
65.
mTOR AND EPILEPTOGENESIS IN DEVELOPMENTAL BRAIN
MALFORMATIONS
835
Michael Wong and Peter B.
Crino
INTRODUCTION
835
ANIMAL MODELS OF mTOROPATHIES: FROM YEAST
TO MICE
836
mTOR ACTIVATION IN HUMAN DEVELOPMENTAL
BRAIN DISORDERS
839
SUMMARY AND FUTURE COURSE
842
Contents xxxv
66. MAJOR
SUSCEPTIBILITY
GENES
FOR COMMON IDIOPATHIC
EPILEPSIES
845
Deb
К
Pal and David A,
Greenberg
INTRODUCTION
845
THE IDIOPATHIC EPILEPSIES AS NEURODEVELOPMENTAL
DISORDERS
846
METHODOLOGICAL ISSUES AND EXPERIMENTAL STRATEGIES
IN COMMON EPILEPSIES
846
ELP4 AND RE
847
Segregation Analysis
·
Linkage Analysis
·
Association Analysis
·
Genomic Resequencing
·
Summary
of Evidence for ELP4 as a Susceptibility Gene for CTS
·
Ehngator Biology
BRD2 AND
JME
851
Segregation Analysis
·
Linkage and Association Analysis
·
Brd2 Knockout Mouse
·
The
Hétérozygote
67.
MYOCLONINl/EFHCl IN CELL DIVISION, NEUROBLAST MIGRATION,
AND SYNAPSE/DENDRITE FORMATION IN JUVENILE MYOCLONIC
EPILEPSY
858
Thierry
Grisar,
Bernard Lakaye, Laurence
de
Nijs, Joseph J. LoTurco, Andrea
Daga,
and
Antonio V.
Delgado-Escueta
EFHCl/MYOCLONINl, A PROTEIN OF UNKNOWN FUNCTION
859
The EF-Hand Motif
·
The DM10 Domains
EFHCl/MYOCLONINl, A
WIDELY DISTRIBUTED PROTEIN
862
EFHCl/MYOCLONINl CALCIUM SIGNALING AND APOPTOSIS
863
EFHCl/MYOCLONINl IN MITOSIS AND CELL DIVISION
864
EFHC1 Colocalizes with Mitotic Spindles
·
EFHC1 Is a Microtubule-Associated Protein
(MAP)
·
EFHC1 Is Required for Mitotic Spindle Organization
·
EFHC1 Impairment Induces
Microtubule Bundling and Apoptosis
EFHCl/MYOCLONIN
1
AND EARLY NEUROBLAST MIGRATION
866
EFHC1 Contributes to Radial Migration and Radial
Glia
Integrity in the Developing
Neocortex
·
EFHC1 Is Essential for Mitosis and Cell Cycle Exit of Cortical Progenitor
Cells
·
EFHC1 Is Required for Locomotion of Postmitotic Neurons
EFHCl/MYOCLONINl, A KEY
CILIAR
COMPONENT PLAYING A ROLE IN THE
FUNCTION OF EPENDYMA
868
THE MAP MYOCLONIN1 IS ESSENTIAL FOR THE NORMAL DEVELOPMENT
AND FUNCTION OF THE NEUROMUSCULAR JUNCTION SYNAPSE
IN
DROSOPHILA
869
EFHC1 OR MYOCLONINl DEFECT CAUSES
JME
AS A DEVELOPMENTAL
DISEASE AFFECTING THE PROPERTIES OF THE MICROTUBULES IN THE
NEURONO-GLIAL PROCESSES AND CORTICAL SYNAPTIC FUNCTIONS
(MICROTUBULOPATHY)
870
CONCLUSIONS
871
xxxvi Contents
68. PROGRESSIVE
MYOCLONUS EPILEPSY OF
LAFORA 874
José M. Serratosa, Berge A. Minassian, and Siibramamam Ganesh
MOLECULAR GENETICS AND GENOTYPE-PHENOTYPE
CORRELATIONS
874
FUNCTIONAL STUDIES: MECHANISMS OF LAFORA BODY FORMATION
AND NEURODEGENERATION
875
MOUSE MODELS BEARING ENGINEERED MUTATIONS IN Epm2A
AND Epm2B
876
69.
PROGRESSIVE MYOCLONUS EPILEPSY: UNVERRICHT-LUNDRORG
DISEASE AND
NEURONAL CEROID
LIPOFUSCINOSES
878
Anna-Elina
Lehesjoki and Mark Gardiner
UNVERRICHT-LUNDBORG DISEASE
878
Clinical Features
·
The Cystatin
В
Gene and Protein
·
EPM
1-Associated Cystatin
В
Gene Mutations
·
CystatinB-Deficient Mouse Model for
EPM
1 ·
Oxidative Stress in
EPM1
·
PRICKLEl and SCARB2 Mutations in EPMl-like Patients
NEURONAL
CEROID LIPOFUSCINOSES
881
CLN1 Disease: PPT1
·
CLN2 Disease: TPP1
·
.CLN3 Disease: CLN3
·
Variant Late Infantile
NCLs: CLN5, CLN6, MFSD8, CLN8
·
CLN
10
Disease: CTSD
·
CLN4 Disease
·
CLN9 Disease
SUMMARY
885
70.
ЄАВВВЗ,
EPILEPSY, AND
NEURODEVELOPMENT
887
Miyabi Tanaka, Timothy M. DeLoretj, Antonio V. Delgado-Escueta, and Richard W.
Olsen
INTRODUCTION
887
BACKGROUND
888
Genomics of GABRB3
·
GABRB3 in Mammalian Brain
Embryogenesis
and Adult
Neurogenesis
·
Epigenetic Modulation of GABRB3
NEURODEVELOPMENTAL DISORDERS
892
GABRBe, Epilepsy, and Autism
·
GABRB3 in Chromosome 15Q11-13, AS, and Prader-Willi
Syndrome
·
GABRB3 and UBE3A in Hippocampus
·
UBE3A and GABRB3 Deficiency with
MeCP2 Dysregulation: RS and AS
CONCLUSIONS
895
71.
PATHOPHYSIOLOGY OF EPILEPSY IN AUTISM SPECTRUM DISORDERS
900
Can
E. Staf
strom,
Paul
J
,
Hagerman, and Isaac
N.
Pessah
INTRODUCTION
900
FRAGILE X SYNDROME
902
Clinical and Genetic Aspects
·
Pathophysiology
·
Treatment Implications
TUBEROUS SCLEROSIS COMPLEX
906
Clinical and Genetic Aspects
·
Pathophysiology
·
Treatment Implications
CONCLUSION: IS THERE A CONVERGENT PATHWAY BETWEEN AUTISM
AND EPILEPSY?
909
Contents xxxvii
72.
COGNITIVE
AND BEHAVIORAL COMORBIDITIES OF EPILEPSY
915
Jonathan K. Kleen, Rod C. Scott, Pierre-Pascal Lenck-Santini,
and Gregory L. Holmes
MECHANISMS OF PERMANENT DEFICITS IN COGNITION
AND BEHAVIOR
916
Permanent Cognitive Deficits
·
Permanent Behavioral Deficits
MECHANISMS OF DYANAMIC DEFICTS IN COGNITION AND BEHAVIOR
920
Dynamic Deficits Secondary to Seizures
·
Dynamic Deficits
Secondar)
to Interictal Spikes
HOW DYNAMIC DEFICITS MAY BECOME PERMANENT
923
Recurrent Seizures
·
Recurrent Interictal Spikes
·
Effect on Behavior
CONCLUSIONS
925
73.
MIGRAINE AND EPILEPSY—SHARED MECHANISMS WITHIN THE FAMILY
OF EPISODIC DISORDERS
930
Michael A.
Rogowski
INTRODUCTION
930
COMORBIDITY OF EPILEPSY AND MIGRAINE
931
Do Migraine Attacks Trigger Seizures?
·
A Hypothesis for Comorbkliry
EPISODIC NEUROLOGICAL DISORDERS
932
FEATURES THAT CHARACTERIZE EPISODIC: DISORDERS
932
ANTIEPILEPTIC DRUGS IN MIGRAINE
933
CORTICAL SPREADING DEPRESSION
934
HYPEREXCITABILITY IN
CSD
AND FOCAL SEIZURES
935
ROLE OF
GLUTAMATE
935
REQUIREMENT FOR SYNAPTIC TRANSMISSION
936
CORTICAL HYPERRESPONSIVITY IN MIGRAINE
936
INSIGHTS FROM GENETICS
938
Calcium Channel
·
Sodium-Potassium Transporter
·
Sodium Channel
CONCLUSIONS
940
74.
NEUBOBIOLOGY OF DEPRESSION AS A COMORBIDITY
OF EPILEPSY
945
Raman Sankar and
Andrey Mazarati
DEPRESSION IN ANIMAL MODELS OF EPILEPSIES
946
DEPRESSION IN AN ANIMAL MODEL OF GENETIC
ABSENCE EPILEPSY
947
DEPRESSION IN ANIMAL MODELS OF LIMBIC EPILEPSY
947
DEPRESSION AFTER KINDLING EPILEPTOGENESIS
947
xxxviii Contents
DEPRESSION
ACCOMPANIES EPILEPTOGENESIS FOLLOWING
SE
950
EPILEPTOGENESIS
IS ACCOMPANIED BY CHANGES IN SEROTONIN
TURNOVER AND EVOKED SEROTONIN RELEASE
950
THE EPILEPTIC STATE AFFECTS THE HYPOTHALAMIC-PITUITARY-
ADRENOCORTICAL
(ΗΡΑ)
AXIS TO PRODUCE EFFECTS ON
SEROTONIN RELEASE
950
INFLAMMATION CONTRIBUTES TO
ΗΡΑ
AXIS DYSREGULATION AND
IMPAIRED SEROTONERGIC FUNCTION AND PROLONGS IMMOBILITY
TIME IN THE FST
952
CONCLUSIONS
954
SECTION
5
EPILEPSY THERAPEUTICS
75.
CALCIUM CHANNEL
α2δ
SUBUNITS IN EPILEPSY AND AS TARGETS FOR
ANTIEPILEPTIC DRUGS
959
Annette C. Dolphin
VOLTAGE-GATED CALCIUM CHANNELS
960
Discovery of Calcium Channels
·
Calcium Channel Purification
·
Calcium Channel
Subunit
Gene Cloning
THE
α2δ
SUBUNITS
961
α2δ
Gene Cloning
·
Classical Topology and Posttranslational Processing of
α2δ
Subunits
·
Novel
Topology: Evidence That
α,δ
Subunits Can Form GPI-Anchored Proteins
·
Structure of
α2δ
Subunits in Calcium Channel Complexes
·
Function of
α2δ
Subunits in Calcium Channel
Complexes
·
Distribution and Function of
се2б
Proteins in Specific Tissues
·
Splice Variants of
(Х2б
Subunits
·
Membrane Localization, Trafficking, and Endocytosis of
α2δ
Subunits
·
Presynaptic
Localization and Transport of
α2δ
Subunits
·
Involvement of
α2δ
Subunits in Synaptogenesis and
Other Processes
·
The
α2δ
Subunits in Disease
MECHANISM OF ACTION OF THE GABAPENTINOID DRUGS ON
α δ
SUBUNITS
966
History of Gabapentinoid Drug Development
·
Effects of Gabapentinoids on Synaptic Transmission
and Transmitter Release
·
Identification of the Gabapentin Receptor in Brain as the
С^б-І
Subunit
·
Acute and Chronic Effects of Gabapentinoids on Calcium Currents
CONCLUSIONS AND FUTURE RESEARCH
968
76.
TARGETING SV2A FOR DISCOVERY OF ANTIEPILEPTIC DRUGS
974
Rafal
M.
Kaminski,
Michel
Giüard,
and
Henrik
ìuitgaard
IDENTIFICATION
OF SV2A AS THE BINDING TARGET FOR LEV
975
BIOLOGY AND FUNCTION OF SV2
975
VALIDATION OF SV2A AS A DRUG TARGET FOR AEDS
976
Affinity-Potency Correlation Studies
·
Anticonvulsant Effects of LEV and Their Relation
to SV2A Occupancy
·
Pharmacology and Phenoryping of SV2A Transgenic Animals in
Seizure Models
Contents xxxix
CHANGES
IN SV2A EXPRESSION IN PRECLINICAL MODELS AND
HUMAN
EPILEPSY
981
CONCLUSION
981
77. NEUROSTEROIDS—
ENDOGENOUS
REGULATORS
OF SEIZURE
SUSCEPTIBILITY AND ROLE IN THE TREATMENT OF EPILEPSY
984
Doodipala Samba Ready and Michael A. Rogawski
INTRODUCTION
984
DIVERSITY OF NEUROSTEROIDS AND THEIR
BIOSYNTHESIS
985
PRODUCTION OF NEUROSTEROIDS IN THE BRAIN AND THEIR
LOCALIZATION TO PRINCIPAL NEURONS
987
NEUROSTEROID MODULATION OF GABAA RECEPTORS
988
ANTICONVULSANT AND ANTIEPILEPTOGENIC EFFECTS
OF NEUROSTEROIDS
990
ROLE OF ENDOGENOUS NEUROSTEROIDS IN THE MODULATION
OF SEIZURES
991
Neurosteroids in Catamenial Epilepsy
·
Neurosteroids and Stress-Induced Seizure
Fluctuations
·
Neurosteroids in Temporal Lobe Epilepsy
·
Neurosteroids and Alcohol
Withdrawal Seizures
GANAXOLONE AS A NOVEL NEUROSTEROID-BASED ANTIEPILEPTIC
DRUG
995
Preclinical Studies
·
Clinical Safety and Efficacy Studies
CONCLUSIONS
997
78.
MECHANISMS OF KETOGENIC DIET ACTION
1003
Susan A. Masino and Jong M. Rho
INTRODUCTION
1003
HISTORICAL AND CLINICAL PERSPECTIVES
1005
Early Hypothesis of KD Action
·
Clinical Insights
ANIMAL MODELS
1006
Acute Models
·
Chronic Animal Models
MECHANISTIC STUDIES IN THE EARLY RENAISSANCE ERA
1007
Ketone
Bodies
·
Age Dependence of
Ketone
Utilization
·
GABAergic
Inhibition
·
Norepinephrine and Neuropeptides
·
Polyunsaturated Fatty Acids
METABOLIC MECHANISMS
1012
KD AND NEUROPROTECTION
1015
FUTURE DIRECTIONS
1015
CONCLUSIONS
1016
xl Contents
79.
DEEP BRAIN STIMULATION FOR EPILEPSY: ANIMAL MODELS
1025
Kevin D.
Graber
and Robert S. Fisher
POTENTIAL MECHANISMS OF ACTION
1026
SITES OF STIMULATION: MODULATION OF THE NETWORK
1026
Cerebellum
·
Basal Ganglia
·
Brainstem
·
Hypothalamus
·
Thalamus
SITES OF STIMULATION: THE SEIZURE FOCUS
1032
Hippocampus and Amygdala
·
Piriform and Entorhinal Cortex
·
Neocortex
LIMITATIONS OF ANIMAL STUDIES
1033
CONCLUSIONS
1034
80.
ANIMAL MODELS FOR EVALUATING ANTIEPILEPTOGENESIS:
ANTIEPILEPTIC DRUGS VERSUS NOVEL APPROACHES
EVALUATED IN POST-STATUS EPILEPTICUS MODELS
OF TEMPORAL LOBE EPILEPSY
1041
H. Steve White
INTRODUCTION
1041
ANIMAL MODELS OF ACQUIRED EPILEPSY
1042
Kindling
·
Status Epilepticus
·
Traumatic Brain Injury
·
Viral Encephalitis
·
Other Models of
Acquired Epilepsy
·
Genetic Models: Unrealized Potential for Therapy Discovery
CHALLENGES IN CHARACTERIZING THE ANTIEPILEPTOGENIC POTENTIAL
OF AN INVESTIGATIONAL THERAPY
1049
CONCLUSIONS
1050
81.
STRATEGIES FOR ANTIEPILEPTOGENESIS
1055
Wolfgang
Löscher
MOST ANTIEPILEPTIC DRUGS ARE NOT ANTIEPILEPTOGENIC
1055
Antiepileptogenesis versus Disease Modification versus Initial Insult Modification
NOVEL APPROACHES FOR ANTIEPILEPTOGENESIS
1059
Neuroprotective Drugs
·
Anti-inflammatory Drugs
· Neuronal
Modulators
CONCLUSIONS
1062
82.
NEONATAL SEIZURES AND
NEURONAL
TRANSMEMBRANE
ION TRANSPORT
1066
Kristopher
T.
Kahle
and Kevin
J. Staley
THE EFFECTS OF
GABA
ARE LAREGLY DETERMINED BY THE
INTRACELLULAR CONCENTRATION OF CHLORIDE
1067
NKCC1 AND KCC2 ARE ESSENTIAL CATION-CHLORIDE COTRANSPORTERS
IN THE NERVOUS SYSTEM
1067
A DEVELOPMENTAL SWITCH IN NKCC1:KCC2 EXPRESSION RENDERS
GABA HYPERPOLARIZING
DURING
NEURONAL
DEVELOPMENT
1068
THE ROLE OF NKCCl-DEPENDENT CHLORIDE ACCUMULATION
IN NEONATAL SEIZURES
1069
Contents xli
TARGETING NKCC1
AND OTHER
CCCS AS AN ANTIEPILEPTIC
STRATEGY
1072
SUMMARY
1073
83. ANTIEPILEPTOGENESIS,
PLASTICITY OF
AED
TARGETS, DRUG
RESISTANCE, AND TARGETING THE IMMATURE BRAIN
1077
Heinz Beck and Yoel Yaari
INTRODUCTION
1077
DEFINING DRUG TARGETS
1078
Sodium Channels
·
Calcium Channels
·
HCN Channels
·
GABAA Receptors
·
Glutamate
Receptors
·
Presynaptic Proteins
·
Unconventional Drug Targets
ALTERED PHARMACOLOGY AND MOLECULAR PLASTICITY OF DRUG
TARGETS IN CHRONIC EPILEPSY
1080
Altered Pharmacology of Voltage-Gated Sodium Channels
·
Plasticity of Calcium Channels:
Emergence of a Novel Drug Target?
·
Plasticity of
Н
-Current Expression: Loss of a Drug
Target?
·
Altered Subunit Composition of GABA^ Receptors
RELATIONSHIP BETWEEN CHANGES IN ANTIEPILEPTIC DRUG TARGETS
AND IN VIVO PHARMACORESISTANCE
1082
RELATIONSHIP BETWEEN THE TARGET AND TRANSPORTER HYPOTHESES
OF PHARMACORESISTANCE
1082
84.
DRUG RESISTANCE
1086
Jan A. Gorier and Heidmn PotscJika
INTRODUCTION
1086
MECHANISMS OF DRUG RESISTANCE
1087
Target Hypothesis
·
Drug Transporter Hypothesis
·
Intrinsic Severity Hypothesis
NOVEL APPROACHES TO OVERCOME DRUG RESISTANCE
1092
APPROACHES TO IDENTIFY RESISTANCE MECHANISMS
IN PATIENTS
1094
SUMMARY
1095
85.
NEURAL STEM CELL THERAPY FOR TEMPORAL LOBE EPILEPSY
1098
Ashok
К
Shetty
EFFICACY OF THE NSC GRAFTING STRATEGY FOR PREVENTING
EPILEPTOGENESIS AND/OR CHRONIC EPILEPSY AFTER
HIPPOCAMPAL INJURY
1099
Effects of Adult Subventricular Zone NSC Grafts in a Unilateral Hippocampal Injury
Model
·
Effects of Intravenous Administration of Human NSCs in
a Pilocarpine
Prototype
of
TLE
·
Effects of Hippocampal NSC Grafts in an
SE
Model
EFFICACY OF NSC GRAFTING FOR EASING CHRONIC
TLE
1102
Effects of NSC Grafts in an SE-Induced Chronic Epilepsy Model
·
Effects of NSC Grafts
in Suppressing SRS in a Kindling Model
CONCLUSIONS AND FUTURE DIRECTIONS
1107
xlii Contents
86.
EMBRYONIC STEM CELL THERAPY FOR INTRACTABLE EPILEPSY
1111
Janice R. Naegele, Mohan C. Veinuri, and
Lorenz Studer
MIGHT STEM CELL THERAPIES BE EFFECTIVE FOR CONTROLLING
SEIZURES IN EPILEPSY?
1112
REPAIRING DYSFUNCTIONAL NEURAL CIRCUITRY IN
TLE
1112
STEM CELLS FOR NEURODEGENERATION AND EPILEPSY
1113
PLURIPOTENT STEM CELLS
1114
INDUCED PLURIPOTENT STEM CELLS
1115
DIRECTED DIFFERENTIATION OF ESCS AND IPSCS
1116
BACTERIAL ARTIFICIAL CHROMOSOME
TRANSGENESIS 1116
CLINICAL GRADE PLURIPOTENT STEM CELLS IN
XENO-
AND FEEDER-FREE
CULTURE SYSTEMS
1116
TRANSPLANT STUDIES OF FETAL NEURAL STEM CELLS FOR SEIZURE
SUPPRESSION IN EXPERIMENTAL MODELS
1117
CHALLENGES IN CELL THERAPY APPROACHES TO TREAT EPILEPSY
1117
CONCLUSIONS AND THE PATH FORWARD
1118
87.
CELL THERAPY USING GABAERGIC NEURAL PROGENITORS
1122
Steivart A. Anderson and Scott C.
Baraban
EMBRYONIC ORIGIN OF CORTICAL
INTERNEURONS
1122
TRANSPLANTATION OF MGE PRECURSOR CELLS
1123
CELL THERAPY USING TRANSPLANTED MGE PRECURSOR CELLS
1123
POTENTIAL SOURCES OF MGE-LIKE
INTERNEURON
PRECURSORS
1125
CONCLUSION
1126
88.
REVERSING DISORDERS OF
NEURONAL
MIGRATION AND
DIFFERENTIATION IN ANIMAL MODELS
1129
Jean-Bernard
Manent
and Joseph
J.
LoTurco
REVERSAL OF A MODEL OF SUBCORTICAL BAND HETEROTOPIA
1129
PHARMACOLOGICAL RESCUE IN A MODEL OF LISSENCEPHALY
1131
REVERSAL OF NEURODEVELOPMENTAL DISRUPTION BEYOND
NEURONAL
MIGRATION DISORDERS
1133
Genetic Rescue of
Rett
Syndrome
·
Pharmacological Rescue of
TSC
SUMMARY AND FUTURE CHALLENGES
1135
Contents xliii
89. GENE
THERAPY OF FOCAL-ONSET EPILEPSY USING ADENO-
ASSOCIATED VIRUS VECTOR-MEDIATED OVEREXPRESSION OF
NEUROPEPTIDE
Y
1139
Francesco
M.
Noè,
Andreas
T.
Scenseti, Merah Kokaia, and
Annamaria
Vezzani
GENE
THERAPY IN
THE CENTRAL
NERVOUS
SYSTEM
AND THE CHOICE
OF TOOLS FOR GENE DELIVERY
1140
GENE THERAPY: THE CHOICE OF THE THERAPEUTIC GENE
1140
THE FOCUS ON NPY
1141
Changes in the Endogenous NPY System during Seizures
GENE THERAPY WITH NPY IN SEIZURE MODELS
1141
AAV-Mediated NPY Overexpression
·
Antieonvulsant Effects Mediated by
Transgene NPY
GENE THERAPY: ANY ADVERSE EFFECTS?
1143
CONCLUSION
1146
90.
ADENOSINE AUGMENTATION THERAPY
1150
Detlev
Botson
ADENOSINE DYSFUNCTION IN EPILEPSY
1151
Astrocytes and Adenosine Kinase Are Key Regulators of Synaptic Adenosine
·
ADK Is a Target
for Seizure Prediction and Prevention
FOCAL ADENOSINE AUGMENTATION
1153
Rationale lor Focal Drug Delivery Approaches in Epilepsy
·
Molecular Approaches to Induce
Adenosine Augmentation
·
Seizure Suppression
unti
Prevention by Focal Adenosine Augmentation
CHALLENGES AND IMPACT
1156
INDEX
1161
he epilepsies are among the most common
severe neurological disorders worldwide,
affecting over fifty million people. The preva¬
lence of epilepsy was one of the myriad reasons
H. Houston Merntt was appointed to chair the
Public Health Service Advisory Committee on the
Epilepsies in
I960
from which a basic research
task force was created, led by Herbert H. Jasper
Since then, basic and clinical researchers in epi¬
lepsy have gathered every
14
years to track the
progress of our understanding of the disorder
and to seek the best methods for prevention and
treatment The editions of this book have arisen
from these gatherings In
1999.
the third edition of
Basic Mechanisms of the Epilepsies was named
m
honor of Jasper
This fourth edition is the most ambitious yet In
90
chapters, the book considers the role of interac¬
tions between neurons, synapses, and
glia
in the
initiation, spread, and arrest of seizures It exam¬
ines mechanisms of excitability, synchronization
seizure susceptibility and ultimately epileptogen-
esis It provides a framework for expanding the
epilepsy
genome
and understanding
lhe
complex
heredity responsible for common epilepsies as i(
explores disease mechanisms of ion channelo-
pathies and developmental epilepsy genes It con¬
siders the mechanisms of epilepsy
comorbiéties
And. for the first time, it
desenhes
the current
efforts to translate the discoveries in epilepsy
As¬
ease
mechanisms into new therapeutic strategies
Long considered the bible of basic epilepsy
research Jaspers
Sasic
Mechanisms of the
Epilepsies fourth Edition rs a must have for the
spileptotogist research scientist clinical scientist
cimicai neuroiogist and student as the »otume not
only provides an encyclopedic coverage of current
understanding but also maps out new research
directions for the next decade
Cower
»nages:
Top left
ЗО
representation of
ine
molecular structure of the
жШерЛерОс
drug
ioewaroate. Too nght: BEG recording Itopt arxi
power spectral densities /bottom;
obtameö
Фжтпд
a seurure from
з
»focarpine-ineated eo^epoc
Odent. image
crem:
Maxime LevesQue.
РЫ)
Bottom
leñ: GUal
пЬгЛшу аскЖ сшет-вптипо-
eacfwe
übers
treat
η
*tvK matter tracts oefweeo
чадросатр*
eyramnJar
ceils and cortical neurons
■
green¡. ¡mage
cree«:
fdwaro
Gťasscoc*.
PN).
flołftyn
Tqht
ftmerte
Ttodéi
ot
ofTořrocc
д
Аащцеа
from May®?
ХО
Jeffrey L Noebels, MD, PhD,
is Cullen
Trust
for
Health
Care Endowed Chair
Professor
of
Neurology,
Neuroscience,
and Molecular and
Human Genetics at Baylor College of Medicine.
He is also vice chair for research and director
of the Blue Bird Circle Developmenta! Neuroge-
netics Laboratory in the Department of Neurol¬
ogy. The focus of his research is on genetic and
cellular mechanisms of
neuronal
synchroniza¬
tion disorders in the developing brain.
Massimo
Avoli,
MD, PhD,
is Professor in the
Department of Neurology and Neurosurgery,
and in the Department of Physiology at Mc-
Gill University. He is also Professor of Human
Physiology at
Sapienza
University of Rome. His
research focuses on the cellular and pharma¬
cological mechanisms underlying excitability
and epileptiform synchronization, epileptogen-
esis, and mental retardation syndromes.
Michael A. Rc-gawski, MD, PhD, is Professor
and Chair of the Department of Netirotogy at
the University of California,
Davis,
School of
Medicine. He previously served as Chief of
the Epilepsy Research Section at the National
Institute of Neurological Disorders and Stroke.
His research is on the cellular mechanisms of
action of antiepileptic drugs and new epttepsy
treatment approaches.
Richard W.
Oteen, PhD,
is Distinguished Pro¬
fessor of
Neuroscience.
Pharmacology, and
Anesthesiology at the David Geffen School of
Medicine. University of California. Los Ange¬
les, in the Department of Molecular and
Medi¬
cai
Pharmacology. The focus of his research ¡s
the structure and function of GABAS receptors
m
the brarn including their involvement in epi¬
lepsy and alcoholism.
Antonio
¥.
Delgado-Escueta.
MO, is Professor
m
residence
m
the Department of Neurology at
the David Geffen School of Medicine. Univer¬
sity of California.
Los Angetes.
He is
ateo
di¬
rector of the
Ериерѕу
Center of Excellence at
the
VA
Greater
Los Angeles
Healthcare System
m
West
Los Angeles-
The focus of
rus
research
is isolating human epilepsy genes and defining
the» disease mechanisms.
|
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| genre_facet | Aufsatzsammlung Konferenzschrift |
| id | DE-604.BV040637053 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T00:28:00Z |
| institution | BVB |
| isbn | 9780199746545 0199746540 |
| language | English |
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| physical | LVII, 1199 S. Ill., graph. Darst. |
| publishDate | 2012 |
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| publisher | Oxford Univ. Press |
| record_format | marc |
| series | Contemporary neurology series |
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| spelling | Jasper's basic mechanisms of the epilepsies ed.: Jeffrey L. Noebels ... Basic mechanisms of the epilepsies 4. ed. New York, NY Oxford Univ. Press 2012 LVII, 1199 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Contemporary neurology series 80 Epilepsie gtt Épilepsie - Congrès ram Épilepsie - Diagnostic Épilepsie - Traitement Épilepsie Epilepsy Epilepsy Congresses Pathology, Cellular Congresses Pathology, Molecular Congresses Epilepsie (DE-588)4015035-5 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content (DE-588)1071861417 Konferenzschrift gnd-content Epilepsie (DE-588)4015035-5 s DE-604 Noebels, Jeffrey L. Sonstige oth Jasper, Herbert H. 1906-1999 Sonstige (DE-588)124328784 oth Contemporary neurology series 80 (DE-604)BV000898796 80 Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025464183&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Klappentext Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025464183&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Jasper's basic mechanisms of the epilepsies Contemporary neurology series Epilepsie gtt Épilepsie - Congrès ram Épilepsie - Diagnostic Épilepsie - Traitement Épilepsie Epilepsy Epilepsy Congresses Pathology, Cellular Congresses Pathology, Molecular Congresses Epilepsie (DE-588)4015035-5 gnd |
| subject_GND | (DE-588)4015035-5 (DE-588)4143413-4 (DE-588)1071861417 |
| title | Jasper's basic mechanisms of the epilepsies |
| title_alt | Basic mechanisms of the epilepsies |
| title_auth | Jasper's basic mechanisms of the epilepsies |
| title_exact_search | Jasper's basic mechanisms of the epilepsies |
| title_full | Jasper's basic mechanisms of the epilepsies ed.: Jeffrey L. Noebels ... |
| title_fullStr | Jasper's basic mechanisms of the epilepsies ed.: Jeffrey L. Noebels ... |
| title_full_unstemmed | Jasper's basic mechanisms of the epilepsies ed.: Jeffrey L. Noebels ... |
| title_short | Jasper's basic mechanisms of the epilepsies |
| title_sort | jasper s basic mechanisms of the epilepsies |
| topic | Epilepsie gtt Épilepsie - Congrès ram Épilepsie - Diagnostic Épilepsie - Traitement Épilepsie Epilepsy Epilepsy Congresses Pathology, Cellular Congresses Pathology, Molecular Congresses Epilepsie (DE-588)4015035-5 gnd |
| topic_facet | Epilepsie Épilepsie - Congrès Épilepsie - Diagnostic Épilepsie - Traitement Épilepsie Epilepsy Epilepsy Congresses Pathology, Cellular Congresses Pathology, Molecular Congresses Aufsatzsammlung Konferenzschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025464183&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025464183&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV000898796 |
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