Untersuchungen zur Rolle des Silent information regulator 2 (Sirt2) im experimentellen Schlaganfall in Mäusen

Investigations about silent information regulator 2 (SIRT2) in experimental stroke in mice

by Lea Farina Magdalena Krey
Doctoral thesis
Date of Examination:2019-08-07
Date of issue:2019-07-22
Advisor:Prof. Dr. George Trendelenburg
Referee:Prof. Dr. George Trendelenburg
Referee:Prof. Dr. Wolfgang Brück
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-7569

 

 

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Abstract

English

Sirtuin-2 (Sirt2) is a member of the NAD+-dependent protein deacetylase family. Various members of the sirtuin class have been found to be involved in processes related to longevity, regulation of inflammation, and neuroprotection. Induction of Sirt2-mRNA was found in the whole hemisphere after experimental stroke in a recent screening approach. Moreover, Sirt2 protein is highly expressed in myelin-rich brain regions after stroke. To examine the effects of Sirt2 on ischemic stroke we induced transient focal cerebral ischemia in adult male Sirt2-knockout- and wild-type mice. Two stroke models with different occlusion times were applied: a severe ischemia (45min of middle cerebral artery occlusion; MCAO) and a mild one (15min MCAO), which was used to focus on subcortical infarcts. Neurological deficit was determined at 48h after 45min of MCAO, and up to 7d after induction of 15min of cerebral ischemia. In contrast to recent data on Sirt1, Sirt2-/-mice showed less neurological deficits in both models of experimental stroke with the strongest manifestation after 48h of reperfusion. However, we did not observe a significant difference of stroke volumes or inflammatory cell count between Sirt2-deficient and wild-type mice. Thus, we postulate that Sirt2 mediates myelin-dependent neuronal dysfunction during the early phase after ischemic stroke.
Keywords: Sirt2; Stroke; MCAO
Schlagwörter: Sirt2; Schlaganfall
 
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