The effects of cilostazol on tissue oxygenation upon an ischemic-reperfusion injury in the mouse cerebrum

Takayuki Morikawa, Katsuji Hattori, Mayumi Kajimura, Makoto Suematsu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Citations (Scopus)

Abstract

Although cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3), is known to exert a potent antiplatelet function by raising intracellular cAMP concentration, its effect on cerebral microcirculation upon an ischemic insult is not clearly understood. To examine effects of cilostazol on the global ischemic injury in the brain, we first measured the plasma leakage using modified Miles assay after mice had been subjected to 60 min of a bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 4 h. Oral treatment with cilostazol (30 mg/kg) significantly increased plasma leakage. This result led us to examine if the treatment with cilostazol recruits more capillaries leading to an increase in surface area for exchange and oxygen transport to tissues. To do so, we simultaneously measured degrees of tissue hypoxia and vessel perfusion. Pimonidazol was injected intraperitoneally 1 h before sacrifice and capillary patency was assessed by fluorescein isothiocyanate-labeled Lycopersicon esculentum lectin bound to the endothelial surface. Treatment with cilostazol markedly increased the capillary patency which was accompanied by a reduction in the hypoxic area.Although the treatment with cilostazol caused an increase in the flux of plasma proteins across endothelial barrier that may imply an adverse role after a BCCA occlusion, this increase in protein leakage was attributable to the increased surface area for exchange which in turn brought about a reduction in tissue hypoxia. Taken together cilostazol appears to produce a protective effect against the ischemic-reperfusion injury.

Original languageEnglish
Title of host publicationOxygen Transport to Tissue XXXI
EditorsEiji Takahashi, Duane Bruley
Pages89-94
Number of pages6
DOIs
Publication statusPublished - 2010 Dec 1

Publication series

NameAdvances in Experimental Medicine and Biology
Volume662
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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