| dc.contributor.advisor | Stadelmann-Nessler, Christine Prof. Dr. | |
| dc.contributor.author | Svehaug, Viviane Rebekka | |
| dc.date.accessioned | 2021-10-25T06:17:40Z | |
| dc.date.available | 2021-11-01T00:50:02Z | |
| dc.date.issued | 2021-10-25 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0008-5954-6 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-8899 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Zeitverlauf und Therapie axonaler Schädigung bei NMO | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | Time course and therapy of axonal damage in NMO | de |
| dc.contributor.referee | Stadelmann-Nessler, Christine Prof. Dr. | |
| dc.date.examination | 2021-10-27 | |
| dc.description.abstracteng | In this doctoral thesis, the time course of axonal damage and the effect of glutamatergic and purinergic receptor antagonists on acute axon pathology were investigated in the focal experimental NMO rat model for the first time. In addition, acute axon destruction was quantified and compared at different stages of activity in human NMO and MS lesions.
Overall, both the animal and human data indicate early-onset axonal damage in NMO, thus underlining the necessity of early optimal and aggressive onset of therapy in this disease, as called for in literature.
Such a therapy is conceivable with NMDA, AMPA/kainate and P2X7 receptor antagonists, which showed a significant reduction of parenchymal axonal damage in the focal NMO animal model. In particular, systemic application of these agents resulted in a strong reduction of perivascular axonal damage in gray matter. Overall, these results support the pathogenetic concept of glutamate and ATP excitotoxicity in NMO.
We also demonstrated that during the course of disease in human NMO, just as in MS, a reduction in acute axonal damage occurs with decreasing lesion activity. There was no significant difference in the extent of axonal damage between corresponding stages of disease activity in NMO and MS.
Further studies should investigate the effect of purinergic and glutamatergic receptor antagonists on axonal damage in different NMO models and with larger samples, as well as the optimal time of application and the clinical correlate of these therapies. Overall, these new insights may provide the basis for the development of new pharmacological treatment options for NMO. | de |
| dc.contributor.coReferee | Odoardi, Francesca Prof. Dr. | |
| dc.subject.eng | MS | de |
| dc.subject.eng | NMO | de |
| dc.subject.eng | axonal damage | de |
| dc.subject.eng | glutamate receptor antagonist | de |
| dc.subject.eng | P2X7 receptor antagonist | de |
| dc.subject.eng | glutamate und ATP excitotoxicity | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0008-5954-6-8 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Medizin (PPN619874732) | de |
| dc.description.embargoed | 2021-11-01 | |
| dc.identifier.ppn | 1775172333 | |
| dc.creator.birthname | Heide | de |