Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to the Pleiotropic Effect of Cilostazol

Abstract

Background and Purpose-Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R). Methods-Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1R␤ expression in the hippocampus was assessed by Western blotting. Results-The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin.Only cilostazol improved motor and cognitive functions with a significant increase (PϽ0.05) in the memory-related IGF-1R-positive ratio and IGF-1R␤ expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels. Conclusions-The

Comprehensive effects of galantamine and cilostazol combination therapy on patients with Alzheimer's disease with asymptomatic lacunar infarction

“…In good agreement with our recent basic study in which cilostazol increased memory‐related insulin‐like growth factor‐1 receptor‐positive cells in the hippocampal CA1 region in stroke‐prone spontaneously hypertensive rats, cilostazol is especially effective on memory retention in patients with AD with asymptomatic lacunar infarction (Fig. ) …”

“…Cilostazol is an antiplatelet agent for preventing CVD, a potent type III phosphodiesterase inhibitor with neuroprotective effects, and improves cognition and regional cerebral flow in patients with AD with CVD and mild cognitive impairment . In addition, we have recently shown that cilostazol protected brains in stroke‐prone spontaneously hypertensive rats …”

Pharmacological Treatment and Prevention of Cerebral Small Vessel Disease: A Review of Potential Interventions

“…Cilostazol was also assessed in chronic lacunar stroke for effects on forearm vascular reactivity , and acute lenticulostriate stroke for neurological deterioration . Experimentally, cilostazol may enhance white matter regeneration after ischemia (Supplement http://onlinelibrary.wiley.com/doi/10.1111/ijs.12466/suppinfo) ; in SHRSP, it both improved motor and cognitive function and reduced infarct size as compared with aspirin . Further trials of cilostazol beyond those listed in Supplementary http://onlinelibrary.wiley.com/doi/10.1111/ijs.12466/suppinfo are thought to be ongoing.…”

Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

“…About 87% of patients with stroke are caused by ischemia, and ischemic stroke is induced by a loss of blood supply to part of the brain [3]. Prevention of ischemic stroke is thus of considerable importance [4,5,6,7], and it should be solved by some antiplatelet drugs, such as aspirin, which are commonly used in daily clinical settings for preventing stroke, recently [8]. …”