Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis: = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Würzburg
2017
|
| Subjects: | |
| Online Access: | Volltext http://d-nb.info/1139641344/34 Inhaltsverzeichnis |
| Physical Description: | 138 Blätter Illustrationen, Diagramme |
| Format: | Langzeitarchivierung gewährleistet, LZA |
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| 100 | 1 | |a Schampel, Andrea |d 1984- |e Verfasser |0 (DE-588)1139730126 |4 aut | |
| 245 | 1 | 0 | |a Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis |b = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose |c submitted by Andrea Schampel from Bonn |
| 246 | 1 | 1 | |a Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose |
| 264 | 1 | |a Würzburg |c 2017 | |
| 300 | |a 138 Blätter |b Illustrationen, Diagramme | ||
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| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Julius-Maximilians-Universität Würzburg |d 2017 | ||
| 538 | |a Langzeitarchivierung gewährleistet, LZA | ||
| 546 | |a Zusammenfassung in deutscher und englischer Sprache | ||
| 650 | 0 | 7 | |a Multiple Sklerose |0 (DE-588)4040693-3 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Nimodipin |0 (DE-588)4136452-1 |2 gnd |9 rswk-swf |
| 653 | |a l-type calcium channel antagonist | ||
| 653 | |a experimental autoimmune encephalomyelitis | ||
| 653 | |a L-typ Calciumkanal Antagonist | ||
| 653 | |a experimentelle autoimmune Enzephalomyelitis | ||
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Record in the Search Index
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| adam_text | TABLE OF CONTENTS
AFFIDAVIT.....................................................................................................................................
5
EIDESSTATTLICHE
ERKLAERUNG........................................................................................................
6
SUMMARY...................................................................................................................................
9
ZUSAMMENFASSUNG..................................................................................................................
10
TABLE OF
CONTENTS.....................................................................................................................
12
LIST OF
ABBREVIATIONS...............................................................................................................
14
I.
INTRODUCTION.....................................................................
19
1.1 MULTIPLE SCLEROSIS
(MS)...................................................................................................
19
1.1.1 ETIOLOGY OF M S
.........................................................................................................
19
1.1.2 CLINICAL
PRESENTATION.................................................................................................
20
1.1.3 PATHOGENESIS OF
MS..................................................................................................
21
1.1.4 PRESENT THERAPEUTIC STRATEGIES FOR M
S.......................................................................23
1.2 THE ROLE OF GLIA CELLS IN NEURODEGENERATIVE
DISEASE.........................................................25
1.3 ANIMAL MODELS OF M S
......................................................................
27
1.3.1 CUPRIZONE
MODEL.......................................................................................................27
1.3.2 THEILER*S MURINE ENCEPHALOMYELITIS VIRUS
(TMEV).................................................28
1.3.3 EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
(EAE)..............................................28
1.3.3.1
INDUCTION................................................................................................................28
1.3.3.2 PHENOTYPES OF EAE
.........................................
29
1.3.3.3 SPECIFICATIONS OF THE MP4 MODEL
.........................................................................
30
1.4 THE ROLE OF CALCIUM IN THE
CNS.......................................................................................31
1.4.1 FUNCTION AND DISTRIBUTION OF VOLTAGE-DEPENDENT CALCIUM CHANNELS
(VDCC) IN THE
CNS...................................................................................................................................31
1.4.2 CA2+ UNDER PATHOLOGICAL CONDITIONS
......................................
34
1.4.2.1 ROLE OF VDCCS IN NEUROLOGICAL
DISORDERS.............................................................34
1.4.2.2 INDICATORS OF CALCIUM-MEDIATED
DAMAGE................................................................35
1.5 THE E-TYPE CALCIUM CHANNEL ANTAGONIST NIMODIPINE AND ITS CNS
APPLICATIONS
..............
36
1.6 AIM OF THIS
STUDY.............................................................................................................37
II. MATERIALS AND
METHODS.....................................................................................................38
II. 1
MICE.........................................................................................................................
38
11.2 EAE INDUCTION AND DRUG
TREATMENT.........................................................................
38
11.3 TISSUE
PREPARATION......................................................................................................41
11.4 SEMI-THIN SECTIONING AND ELECTRON MICROSCOPY
.....................................
42
11.5
IMMUNOHISTOCHEMISTRY...............................................................................................44
11.6
IMMUNOCYTOCHEMISTRY................................................................................................
46
11.7 ROS
DETECTION............................................................................................................
47
II. 8 RNA EXTRACTION, RT-PCR AND MICROARRAY
ANALYSES................................................... 48
II.9 CELL
CULTURE.................................................................................................................
51
II. 10 MICROGLIA ISOLATION AND
CULTIVATION...........................................................................
52
II. 11 FLOW
CYTOMETRY........................................................................................................
53
11.12 PATCH
CLAMP..............................................................................................................
54
11.13
IMMUNOBLOTTING........................................................................................................
54
11.14 SLICE CULTURE AND
STAINING.........................................................................................
55
11.15
STATISTICS...................................................................................................................
57
III.
RESULTS...............................................................................................................................
58
III. 1 NIMODIPINE TREATMENT SIGNIFICANTLY ATTENUATED CLINICAL COURSE OF
EAE
................
58
111.2 NIMODIPINE TREATMENT DECREASED NEURODEGENERATION AND INCREASED
REMYELINATION.. 62
III. 3 NIMODIPINE TREATMENT PROTECTS OLIGODENDROCYTES FROM EAE-INDUCED
LOSS
...........
65
111.4 THE EXTENT OF INFLAMMATION DID NOT DIFFER BETWEEN TREATMENT GROUPS
.....................
67
111.5 NIMODIPINE TREATMENT RESULTED IN DECREASED CELL VIABILITY,
SHRINKAGE, AND APOPTOSIS
OF MICROGLIAL
CELLS.............................................................................................................
72
111.6 NIMODIPINE INDUCED A DECREASE IN NO PRODUCTION AND INOS EXPRESSION
IN MICROGLIA
AND SPINAL CORD AND WAS ACCOMPANIED BY DECREASED ROS IN VIVO
....................................
83
111.7 EFFECTS OF NIMODIPINE TREATMENT ON MICROGLIA ARE INDEPENDENT OF
CAV 1.2 CHANNEL
BLOCKAGE............................................................................................................................88
IV.
DISCUSSION.........................................................................................................................90
IV. 1 STUDY DESIGN AND SUMMARY OF THE
RESULTS.............................................................. 90
IV.2 EFFECTS ON
INFLAMMATION...........................................................................................91
IV.3 EFFECTS ON NERVE FIBER
HISTOPATHOLOGY.......................................................................92
IV.4 EFFECTS ON GLIAL
CELLS..................................................................................................95
IV.5 ADDITIONAL ALTERATIONS IN GENE
EXPRESSION.................................................................99
IV.6 OUTLOOK AND FUTURE
STUDIES......................................................................................
102
IV.7 CONCLUDING
REMARKS................................................................................................
105
V.
REFERENCES.......................................................................................................................
107
VI.
ANNEX..............................................................................................................................131
ACKNOWLEDGMENTS..............................................................................................................
131
PUBLICATIONS
LIST...................................................................................................................
133
CURRICULUM VITAE ANDREA
SCHAMPEL...................................................................................
135
|
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| spelling | Schampel, Andrea 1984- Verfasser (DE-588)1139730126 aut Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose submitted by Andrea Schampel from Bonn Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose Würzburg 2017 138 Blätter Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Julius-Maximilians-Universität Würzburg 2017 Langzeitarchivierung gewährleistet, LZA Zusammenfassung in deutscher und englischer Sprache Multiple Sklerose (DE-588)4040693-3 gnd rswk-swf Nimodipin (DE-588)4136452-1 gnd rswk-swf l-type calcium channel antagonist experimental autoimmune encephalomyelitis L-typ Calciumkanal Antagonist experimentelle autoimmune Enzephalomyelitis (DE-588)4113937-9 Hochschulschrift gnd-content Nimodipin (DE-588)4136452-1 s Multiple Sklerose (DE-588)4040693-3 s DE-604 Erscheint auch als Online-Ausgabe, PDF urn:nbn:de:bvb:20-opus-148952 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-148952 Resolving-System kostenfrei Volltext http://d-nb.info/1139641344/34 Langzeitarchivierung Nationalbibliothek DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029885126&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Schampel, Andrea 1984- Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose Multiple Sklerose (DE-588)4040693-3 gnd Nimodipin (DE-588)4136452-1 gnd |
| subject_GND | (DE-588)4040693-3 (DE-588)4136452-1 (DE-588)4113937-9 |
| title | Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose |
| title_alt | Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose |
| title_auth | Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose |
| title_exact_search | Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose |
| title_full | Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose submitted by Andrea Schampel from Bonn |
| title_fullStr | Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose submitted by Andrea Schampel from Bonn |
| title_full_unstemmed | Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose submitted by Andrea Schampel from Bonn |
| title_short | Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis – an animal model for multiple sclerosis |
| title_sort | beneficial therapeutic effects of the l type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis an animal model for multiple sclerosis gunstige therapeutische effekte des l typ calciumkanal antagonisten nimodipin in der experimentellen autoimmunen enzephalomyelitis einem tiermodell der multiplen sklerose |
| title_sub | = Günstige therapeutische Effekte des L-Typ-Calciumkanal-Antagonisten Nimodipin in der experimentellen autoimmunen Enzephalomyelitis ̶ einem Tiermodell der Multiplen Sklerose |
| topic | Multiple Sklerose (DE-588)4040693-3 gnd Nimodipin (DE-588)4136452-1 gnd |
| topic_facet | Multiple Sklerose Nimodipin Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-148952 http://d-nb.info/1139641344/34 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029885126&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT schampelandrea beneficialtherapeuticeffectsoftheltypecalciumchannelantagonistnimodipineinexperimentalautoimmuneencephalomyelitisananimalmodelformultiplesclerosisgunstigetherapeutischeeffektedesltypcalciumkanalantagonistennimodipininderexperimentellenautoimmunenenzephalo AT schampelandrea gunstigetherapeutischeeffektedesltypcalciumkanalantagonistennimodipininderexperimentellenautoimmunenenzephalomyelitiseinemtiermodelldermultiplensklerose |