Protective effects of cilostazol against transient focal cerebral ischemia and chronic cerebral hypoperfusion injury.
Cilostazol increases intracellular cyclic adenosine monophosphate (cyclic AMP) levels by inhibiting type III phosphodiesterase. It was approved by the Food and Drug Administration for the treatment of intermittent claudication. Its principal actions include inhibition of platelet aggregation, antithrombotic action in cerebral ischemia, and vasodilation, mediated by increased cyclic AMP levels. In a multicenter, randomized, placebo-controlled, double-blind clinical trial, cilostazol has been shown to protect patients from recurrent cerebral infarction. It has been recently suggested that cilastozol could be useful in the treatment of transient focal cerebral ischemic injury. Beneficial effects of cilostazol in cerebral ischemic infarction and edema formation has been confirmed in rats by the magnetic resonance imaging (MRI). The preventive effect was ascribed to cAMP-dependent protein kinase (PKA)-coupled maxi-K channel activation with additional antioxidant and poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitory actions. Most recently, cilostazol has been shown to prevent vacuolation and rarefaction in the white matter of the rats subjected to chronic cerebral hypoperfusion in association with suppression of astrocyte and microglial activation. Taken together, recent experimental studies with cilostazol showed promising results in cerebral ischemia and chronic cerebral hypoperfusion.
Lee
Jeong Hyun
JH
Department of Pharmacology, College of Medicine, Pusan National University, Busan, Korea.
Park
So Youn
SY
Shin
Hwa Kyoung
HK
Kim
Chi Dae
CD
Lee
Won Suk
WS
Hong
Ki Whan
KW
D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D002908:Chronic Disease; D000077407:Cilostazol; D002986:Clinical Trials as Topic; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D013777:Tetrazoles; D000077407:Cilostazol