Der Einfluss der Fettsäuresynthese auf die neuronale Schädigung nach Hypoxie und zerebraler Ischämie

by Lisa Marie Janssen
Doctoral thesis
Date of Examination:2022-04-20
Date of issue:2022-04-22
Advisor:Prof. Dr. Thorsten Roland Döppner
Referee:Prof. Dr. Thorsten Roland Döppner
Referee:Prof. Dr. André Fischer
Persistent Address: http://dx.doi.org/10.53846/goediss-9184

 

 

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Abstract

English

In the context of a stroke, a cascade of reactions is induced at the cellular level, resulting in inflammation and apoptosis. Fatty acids play a pivotal role in cell metabolism - they can be generated de novo from carbon or taken up via blood stream. Fatty acids play only a minor role in the central nervous system in terms of nutrition, but they are involved in the regulation of inflammation and apoptosis. As a result, the regulation of fatty acids suggests a possible adaptation mechanism of neurons to hypoxic conditions. This thesis aims to shed more light on that aspect. Methodologically, the treatment of SH-SY5Y cells and primary cortex cells with combined oxygen and glucose deprivation represented a valid stroke model for in vitro experiments, in vivo cerebral ischemia was induced using the middle cerebral artery occlusion model in mice. The two inhibitors cerulenin and 5-(tetradecyloxy)-2-furoic acid (TOFA) were used to modulate fatty acid synthesis. In the course of this, it was shown for the first time that the inhibition of fatty acid synthesis both in vitro and in vivo is associated with an aggravation of acute cell damage and increased infarct volume after cerebral ischemia. At the same time, inhibition of fatty acid synthesis has a negative effect on neurological recovery after cerebral ischemia. In addition to acute cell damage, metabolic metabolites were examined. Although no change in the quantification of free fatty acids was detected, the inhibition of fatty acid synthesis limits the reduction potential, which in turn modulates various metabolic pathways. When considering the post-ischemic glial and microglial reaction in terms of a central inflammatory reaction, a tendency towards increased activation of these cells could be observed. Overall, it could be shown that fatty acid synthesis and its modulation plays an important role in the adaptation to hypoxic/ischemic conditions in neurons.
Keywords: cerebral ischemia, fatty acid synthesis, neurological recovery
Schlagwörter: Zerebral Ischämie, Fettsäuresynthese
 
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