| dc.contributor.advisor | Ehrenreich, Hannelore Prof. Dr. Dr. | de |
| dc.contributor.author | Hagemeyer, Nora | de |
| dc.date.accessioned | 2013-01-14T15:07:17Z | de |
| dc.date.available | 2013-01-30T23:50:52Z | de |
| dc.date.issued | 2012-06-14 | de |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-000D-EF5E-D | de |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-1472 | |
| dc.description.abstract | Neuroprotektive und neuroregenerative
Eigenschaften von Erythropoietin (EPO) wurden u.a. in Modellen der
experimentellen autoimmunen Enzephalomyelitis (etablierte
Tiermodelle zur Untersuchung der Multiplen Sklerose (MS)) und in
Patienten mit chronisch-progredienter MS nachgewiesen. Der
Wirkmechanismus von EPO bei diesen Bedingungen ist allerdings noch
nicht vollst | de |
| dc.format.mimetype | application/pdf | de |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | de |
| dc.title | Effects of recombinant human erythropoietin in the cuprizone mouse model of de- and remyelination | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | Wirkungen von rekombinantem humanen Erythropoietin im Cuprizone-Maus-Modell | de |
| dc.contributor.referee | Ehrenreich, Hannelore Prof. Dr. Dr. | de |
| dc.date.examination | 2012-05-18 | de |
| dc.subject.dnb | 570 Biowissenschaften, Biologie | de |
| dc.subject.gok | WA000 | de |
| dc.description.abstracteng | Erythropoietin (EPO) has potent
neuroprotective/neuroregenerative properties in various forms of
experimental autoimmune encephalomyelitis (EAE), i.e. established
rodent models of acute multiple sclerosis (MS), and in patients
suffering from chronic progressive MS. However, the mechanisms of
EPO action in these conditions is still not clear. In particular,
studies on potential effects of EPO on oligodendrocytes/myelin in
the absence of immune-inflammatory components, which are
characteristic for acute MS but not for the chronic progressive
state of the disease, are lacking. Therefore, in this PhD thesis,
the cuprizone mouse model was employed to investigate the effect of
EPO on toxic demyelination. This model allows investigation of
myelination processes independent of T-cell mediated inflammation.
Feeding of mice with 0.2% cuprizone mixed into ground chow results
in demyelination of the corpus callosum, whereas withdrawal of the
toxin leads to spontaneous remyelination. The hypothesis of the
present thesis was that EPO modulates both, cuprizone-induced
demyelination and the remyelination upon toxin-withdrawal. Two
study designs were chosen to investigate the effects of EPO in a
clinically most relevant manner: (1) EPO treatment was started
immediately after cessation of 6 weeks of cuprizone feeding, i.e.
at the time point of full damage and initiation of
recovery/remyelination, or (2) EPO was given after 3 weeks of toxin
application and continued for 3 weeks until cessation of cuprizone
feeding to catch the demyelination phase. For both study parts, a
'double-blind' (for food/injections), placebo-controlled,
longitudinal 4-arm design, using 8 week old male C57BL/6 mice, was
applied. Target parameters included behavioral analyses, magnetic
resonance imaging, and histology, as well as measurement of protein
and mRNA levels. The cuprizone mouse model emerged as a highly
variable animal model, making deeper mechanistic analyses of EPO
effects difficult. Despite these limitations and a lack of clear
effects of EPO on remyelination, EPO showed surprisingly distinct
results when applied during the demyelination phase. Immediately
after termination of cuprizone feeding, EPO revealed beneficial
effects on vestibulomotor function/coordination, magnetic resonance
imaging readouts and inflammation, as reflected by the number of
microglia in the corpus callosum. Importantly, for the first time,
EPO was found to reduce axonal degeneration in brain white matter
tracts. These findings are of high relevance with respect to novel
treatment strategies for demyelinating diseases such as MS. | de |
| dc.contributor.coReferee | Bayer, Thomas A. Prof. Dr. | de |
| dc.subject.topic | Biology (incl. Psychology) | de |
| dc.subject.ger | Erythropoietin | de |
| dc.subject.ger | Cuprizone | de |
| dc.subject.ger | Axonale Degeneration | de |
| dc.subject.ger | Mikrogliazellen | de |
| dc.subject.ger | Magnetresonanztomographie | de |
| dc.subject.ger | Mausverhalten | de |
| dc.subject.eng | erythropoietin | de |
| dc.subject.eng | cuprizone | de |
| dc.subject.eng | axonal degeneration | de |
| dc.subject.eng | microglia | de |
| dc.subject.eng | magnetic resonance imaging | de |
| dc.subject.eng | mouse behavior | de |
| dc.subject.bk | 42.63 | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-webdoc-3561-5 | de |
| dc.identifier.purl | webdoc-3561 | de |
| dc.affiliation.institute | Biologische Fakultät | de |
| dc.identifier.ppn | 719297745 | de |