Cilostazol attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.
OBJECTIVE
Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Cilostazol, a selective inhibitor of phosphodiesterase 3, is a peripheral vasodilator, an anti-inflammatory, and causes antiplatelet aggregation.  We investigated these effects on cerebral vasospasm after rat SAH.


METHODS
Thirty-eight Sprague-Dawley rats were randomly divided into three groups: SAH + normal feed (SAH group; n=14), SAH + feed containing 0·1% cilostazol (cilostazol group; n=12) and  sham-operated rats (sham group; n=12). The basilar arteries (BA) of all groups were analysed by measuring wall thickness, internal luminal perimeter and cross-sectional area on day 7. Immunohistochemical study with RM-4, an anti-rat macrophage/dendritic cells monoclonal antibody and  ultrastructural study with transmission electron microscopy were performed.


RESULTS
Although most animals in the SAH group presented with typical vasospasm, the means of inner perimeter and cross-section area of the BA in the cilostazol group were significantly greater than the  SAH group (836 ± 134 μm versus 771 ± 125 μm and 39 177 ± 15 405 μm(2) versus 33 098 ± 13 871 μm(2), respectively). Wall thickness of the BA in the cilostazol group demonstrated significant decrease, compared with the SAH group (17·4  ± 2·3 versus 21·0 ± 2·7 μm). In immunohistological study, SAH induced an obvious increase in mean perivascular RM-4-positive cell count, whereas cilostazol significantly reduced it by 59%. Ultrastructural study depicted cilostazol markedly attenuating  structural deterioration of the vascular wall due to SAH.


CONCLUSIONS
This work demonstrates that cilostazol attenuates cerebral vasospasm after SAH in rat, possibly in part due to the anti-inflammatory effect.
Nishino
Akio
A
Department of Neurosurgery, Osaka University Faculty of Medicine, Osaka, Japan.
Umegaki
Masao
M
Fujinaka
Toshiyuki
T
Yoshimine
Toshiki
T
D000818:Animals; D000077407:Cilostazol; D004195:Disease Models, Animal; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013777:Tetrazoles / Q000627:therapeutic use*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D018696:Neuroprotective Agents; D013777:Tetrazoles; D000077407:Cilostazol