title: Knockout of silent information regulator 2 (SIRT2) preserves neurological function after experimental stroke in mice.
abstract: 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 (45 minutes of middle cerebral artery occlusion (MCAO)) and a mild one (15 minutes of MCAO), which was used to focus on subcortical infarcts. Neurological deficit was determined at 48 hours after 45 minutes of MCAO, and up to 7 days after induction of 15 minutes 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 48 hours 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.
authors.affiliation: Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Krey
authors.affiliation: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Fred
authors.initials: F
authors.lastname: Lühder
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kusch
authors.affiliation: Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Bozena
authors.initials: B
authors.lastname: Czech-Zechmeister
authors.affiliation: Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Könnecke
authors.affiliation: Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Department of Neurodegeneration and Restorative Research, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Tiago
authors.initials: T
authors.lastname: Fleming  Outeiro
authors.affiliation: Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: George
authors.initials: G
authors.lastname: Trendelenburg
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D002452:Cell Count; D015870:Gene Expression; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015427:Reperfusion Injury / Q000473:pathology; D056565:Sirtuin 2 / Q000235:genetics*; D037761:Sirtuins / Q000096:biosynthesis; D020521:Stroke / Q000150:complications / Q000235:genetics* / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2; D037761:Sirtuins