Cilostazol increases collateral remodeling and reduces the severity of ischemic stroke

The need to identify therapies capable of increasing collateral blood flow after stroke has recently come into focus. This study examined the idea of repurposing an already FDA-approved drug for a new indication-inducing collaterals to remodel to larger diameters after acute stroke. We tested cilostazol, an agent whose molecular mechanism of action suggested such a capability. Importantly, cilostazol is currently used to reduce the incidence of recurrent stroke and transient ischemic attack. In mice with abundant collaterals at baseline, 7-day administration of cilostazol at the dose used clinically beginning 2 h after obstruction of the MCA, boosted collateral growth, that is, anatomic lumen diameter, such that the increase in relative collateral flow post-stroke was augmented by 31% (p = 0.004) 48 h after occlusion. The effect was stronger in mice with poor collaterals, 275% (p = 0.018), in association with a significant decrease in infarct volume and improved functional outcome. Moreover, when combined with an experimental drug that acts by a complimentary mechanism vis-a-vis cilostazol, mice with poor collaterals experienced an additive 261% (p = 0.007) additional increase 7 days post-occlusion. Cilostazol's augmentation of remodeling extended to mice with advanced age or diabetes. This study provides a basis for further pre-clinical as well as clinical investigation.