Cilostazol alleviates white matter degeneration caused by chronic cerebral hypoperfusion in mice: Implication of its mechanism from gene expression analysis

Neuroscience Letters
Ryo OhtomoAtsushi Iwata

Abstract

Cilostazol is known to alleviate white matter demyelination due to chronic cerebral hypoperfusion in rodent models, although their pharmacological mechanisms remain unclear. In this study, we investigated the protective effect of cilostazol in relation to gene expression profile. Bilateral common carotid artery stenosis (BCAS) mice were treated with oral administration of cilostazol or placebo starting from a week after the surgery. Demyelination of the cingulum was compared between the 2 groups 2, 6, and 10 weeks after initial drug administration. Also, to examine temporal gene expression change during demyelination, DNA microarray analysis was conducted using samples from the corpus callosum of 2nd and 6th week BCAS mice. For genes that showed more than 2-fold up-regulation, their increase was validated by qPCR. Finally, to determine the effect of cilostazol towards those genes, their expression in the corpus callosum of 6-week placebo-treated and cilostazol-treated BCAS mice was compared by qPCR. Amelioration of myelin loss was observed in cilostazol-treated group, showing significant difference with those observed in placebo group after 10-week treatment. Gene ontology analysis of the 17 up-regulated (FDR<0.01) genes showed...Continue Reading

Citations

Mar 5, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Baoqiang LiSava Sakadžić
Jun 14, 2018·International Journal of Molecular Sciences·Ryo OhtomoKen Arai
Nov 23, 2019·Stroke; a Journal of Cerebral Circulation·Eric E Smith, Hugh S Markus
Jul 6, 2021·Frontiers in Cell and Developmental Biology·Hajime TakaseKen Arai

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