Untersuchungen zum präventiven und therapeutischen Potential von medizinischem Ozon im Superoxid-Dismutase-G93A Mausmodell der amyotrophen Lateralsklerose

Die amyotrophe Lateralsklerose (ALS) ist eine primär neurodegenerative Erkrankung, die Motoneurone des primären Motorcortex, des corticospinalen Trakts, des Hirnstamms und des Rückenmarks betrifft. ALS Patienten entwickeln in einem Zeitraum von 3-5 Jahren Lähmungserscheinungen in der Muskulatu...

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Bibliographic Details
Main Author: Kresse, Carolin
Contributors: Schütz, B. (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2019
Online Access:PDF Full Text
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Amyotrophic lateral sclerosis (ALS) primarily is a neurodegenerative disease affecting motor neurons of the primary motor cortex, corticospinal tract, brainstem and spinal cord. ALS patients develop paralysis in the muscles of the extremities and die from respiratory paralysis over a period of 3-5 years. Despite intensive research, no drug with significant life-prolonging or therapeutic effects could be implemented more than 150 years after the initial description. Only animal models - among them the far best characterized SOD1 G93A mouse model - made it possible to gain a deeper understanding of the pathomechanisms of ALS and thus offer starting points for the development of new therapies. Frequently discussed pathological processes in ALS are oxidative stress and neuroinflammatory mechanisms. The pathological effect factor of oxidative stress served as a therapeutic target for the treatment of SOD1-G93A mice by peritoneal insufflation of an O3/O2 gas mixture. Ozone has a strong oxidative effect and thus influences the redox balance. Experimental studies in which i.p. O3/O2 treatment was applied showed modulating effects on the immune system of the respective model organisms. This led to the hypothesis that repetitive i.p. O3/O2 treatment could attenuate the damaging oxidative mechanisms in the ALS disease process and induce protective immune responses in SOD1-G93A mice. In the present work, the SOD1-G93A mouse model was used as a model organism to characterize preventive and therapeutic O3/O2 treatment for the onset, progression, and lifespan of animals. Percentage distributions of immune cell subpopulations in blood, spleen and mesenteric lymph nodes during disease progression were measured by FACS analysis. Attenuations of neurodegenerative processes in the brainstem were documented by MRI analysis. All results indicate the ineffectiveness of O3/O2 treatment on the course of ALS, including disease start point, reductions in motor abilities, and life span. On the immunological level no changes in the distribution of the immune cell subpopulations were detectable, while MRI visible lesions in the brainstem of the SOD1-G93A mice remained unaffected by the treatment. Only further analyses, based on the cell and tissue samples collected in this study, will show whether O3/O2 therapy in connection with ALS disease can be regarded as a meaningful therapy option, for which it is worthwhile to carry out further research, e.g. on the form of application, duration or time of intervention.