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Dock, Hua
Publications (2 of 2) Show all publications
Ingberg, E., Dock, H., Theodorsson, E., Theodorsson, A. & Ström, J. O. (2016). Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis. Scientific Reports, 6
Open this publication in new window or tab >>Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed) Published
Abstract [en]

Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specifi c pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters’ impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
National Category
Clinical Medicine Microbiology in the medical area
urn:nbn:se:liu:diva-123892 (URN)10.1038/srep21086 (DOI)000370034300001 ()

Funding agencies:  County Council of Ostergotland, Sweden

Vid tiden för disputation förelåg publikationen endast som manuskript

Available from: 2016-01-13 Created: 2016-01-13 Last updated: 2019-12-20Bibliographically approved
Dock, H., Theodorsson, A. & Theodorsson, E. (2015). DNA Methylation Inhibitor Zebularine Confers Stroke Protection in Ischemic Rats. TRANSLATIONAL STROKE RESEARCH, 6(4), 296-300
Open this publication in new window or tab >>DNA Methylation Inhibitor Zebularine Confers Stroke Protection in Ischemic Rats
2015 (English)In: TRANSLATIONAL STROKE RESEARCH, ISSN 1868-4483, Vol. 6, no 4, p. 296-300Article 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
Zebularine; DNA methylation inhibitor; Ischemic stroke; Neuroprotection
National Category
Clinical Medicine
urn:nbn:se:liu:diva-120207 (URN)10.1007/s12975-015-0397-7 (DOI)000357040400007 ()25824538 (PubMedID)

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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