Axonale Schädigung und Makrophageninfiltration bei Entmarkungserkrankungen

by Anna Kristin Dannenberg
Doctoral thesis
Date of Examination:2025-08-14
Date of issue:2025-07-14
Advisor:Prof. Dr. Christine Stadelmann-Nessler
Referee:PD Dr. Jan C. Koch
Referee:Prof. Dr. Dr. Philipp Kauffmann
Persistent Address: http://dx.doi.org/10.53846/goediss-11383

 

 

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Abstract

English

Even though the etiology of multiple sclerosis (MS) has been of scientific interest for a long time, it still remains unclear what exactly causes the axonal damage leading to neurological dysfunction. Especially since pathological changes can also be found in normal appearing white matter (NAWM) of visually intact myelin. Therefore, this study uses different immunohistochemical markers to point out the range of phagocytic and lymphocytic inflammation as well as the extent of axonal damage within demyelinated lesions, periplaque white matter (PPWM) and NAWM of MS patients and for comparative reasons of NMO and PML patients. A cohort of 25 MS patients (3 autopsies, 22 biopsies), 8 NMO patients (5 autopsies, 3 biopsies), 15 PML patients (11 autopsies, 4 biopsies) and a control group (6 autopsies, 5 biopsies) have been analyzed for this purpose. The inflammatory activity in terms of macrophage infiltration and microglia activation was mostly measurable in lesions and PPWM, although there has also been an increased number of inflammatory cells in the NAMW. To analyze the extent of axonal damage two different markers have been examined. Disruptions in axonal transport detected by the amyloid precursor protein (APP) have only been slightly increased in the NAWM whereas non-phosphorylated neurofilament (SMI32) was especially measurable in the PPWM and NAWM of MS and NMO patients. In conclusion, those findings bring up the question if the axonal damage in MS only derives from the demyelinating process so that further investigations regarding pre-lesional axonal pathologies might be useful for diagnostic and therapeutic purposes.
Keywords: multiple sclerosis; normal appearing white matter; axonal damage; SMI32; demyelination
 
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