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DNA Methylation Inhibitor Zebularine Confers Stroke Protection in Ischemic Rats
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
2015 (English)In: TRANSLATIONAL STROKE RESEARCH, ISSN 1868-4483, Vol. 6, no 4, 296-300 p.Article in journal (Refereed) Published
Abstract [en]

5-Aza-deoxycytidine (5-aza-dC) confers neuroprotection in ischemic mice by inhibiting DNA methylation. Zebularine is another DNA methylation inhibitor, less toxic and more stable in aqueous solutions and, therefore more biologically suitable. We investigated Zebularines effects on brain ischemia in a rat middle cerebral artery occlusion (MCAo) model in order to elucidate its therapeutic potential. Male Wistar wild-type (WT) rats were randomly allocated to three treatment groups, vehicle, Zebularine 100 mu g, and Zebularine 500 mu g. Saline (10 mu L) or Zebularine (10 mu L) was administered intracerebroventricularly 20 min before 45-min occlusion of the middle cerebral artery. Reperfusion was allowed after 45-min occlusion, and the rats were sacrificed at 24-h reperfusion. The brains were removed, sliced, and stained with 2 % 2,3,5-triphenyltetrazolium chloride (TTC) before measuring infarct size. Zebularine (500 mu g) reduced infarct volumes significantly (p less than 0.05) by 61 % from 20.7 +/- 4.2 % in the vehicle treated to 8.1 +/- 1.6 % in the Zebularine treated. Zebularine (100 mu g) also reduced infarct volumes dramatically by 55 to 9.4 +/- 1.2 %. The mechanisms behind this neuroprotection is not yet known, but the results agree with previous studies and support the notion that Zebularine-induced inhibition of DNA methyltransferase ameliorates ischemic brain injury in rats.

Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2015. Vol. 6, no 4, 296-300 p.
Keyword [en]
Zebularine; DNA methylation inhibitor; Ischemic stroke; Neuroprotection
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-120207DOI: 10.1007/s12975-015-0397-7ISI: 000357040400007PubMedID: 25824538OAI: oai:DiVA.org:liu-120207DiVA: diva2:842698
Note

Funding Agencies|County Council of Ostergotland, Sweden

Available from: 2015-07-21 Created: 2015-07-20 Last updated: 2015-07-21

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Dock, HuaTheodorsson, AnnetteTheodorsson, Elvar
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Division of Microbiology and Molecular MedicineFaculty of Medicine and Health SciencesDivision of Neuro and Inflammation ScienceDepartment of NeurosurgeryDepartment of Clinical Chemistry
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