Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Haindl, M.
Mechanisms of neuroprotection and repair following immune mediated tissue damage
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2019. pp.70.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Fazekas Franz
- Hochmeister Sonja
- Wonisch Willibald
- Altmetrics:
- Abstract:
- Neuroprotection describes the prevention of damage to nerve tissue via pharmacological or molecular biological methods with the aim to influence the course of the disease and improve the quality of life for patients. In order to reach this aim it is necessary to investigate the cellular background of the respective diseases to allow to intervene at distinct cellular pathways. This thesis focused on the mechanisms of tissue damage and repair in Multiple Sclerosis (MS). MS is an inflammatory demyelinating disease of the central nervous system mainly affecting young adults. Most patients start with a relapsing-remitting (RR) disease phase and enter a secondary progressive (SP) phase after a duration of approximately 25 years. Histologically, these disease stages are very different. To investigate cellular characteristics of RRMS and SPMS two different animal models were used, hence this thesis comprises two separate projects. The methods used included immunohistochemistry, colorimetric testing, enzyme-linked immunosorbent assays and in-situ hybridization. In the first project, a common animal model for MS, the experimental autoimmune encephalomyelitis (EAE), which resembles the cellular characteristics of human RRMS quite well, was used. The investigation focused on (reactive) astrocytes and the biological characteristics of the glial scar and its influence on repair processes after inflammatory demyelination. Most often the glial scar is thought of an impenetrable barrier to remyelinating oligodendrocytes, hindering any repair. In our study however we were able to show that at least in this animal model of EAE the formation of a glial scar does not prohibit remyelination but actually can even facilitate repair. In the second project a new animal model, the cortical lesions model (CLM), which resembles most of the cellular characteristics of human SPMS brain pathology, was established. Apart from establishing the model, CLM was used to investigate the role of oxidative stress and the effect of vitamin D (vitD) supplementation on cortical pathology. It is demonstrated that in this CLM model vitD has a protective effect and ameliorates the disease course at least when the animals receive a preventive vitD supplementation right after weaning from their mothers. This thesis resulted in two main novel findings. It allows a new view of the glial scar and might lead to new neuroprotective strategies by enhancing astrocytic factors in different stages of repair. Secondly, this thesis introduces a new animal model reassembling many features of cortical pathology of human SPMS and offers the opportunity to test potentially neuroprotective and repair- facilitating agents directly in the brain lesions. Additionally the promising findings on vitD suggest further research to identify ways to therapeutically use vitD supplementation for SPMS patients.