Neuroprotection by cilostazol, a phosphodiesterase type 3 inhibitor, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion

• Published in: Brain research 2006-04, Vol.1082 (1), p.182-191
• Main Authors: Lee, Jeong Hyun, Park, So Youn, Shin, Yung Woo, Hong, Ki Whan, Kim, Chi Dae, Sung, Sang-Min, Kim, Ki Young, Lee, Won Suk
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Apoptosis - drug effects; Biological and medical sciences; Brain - pathology; Brain Ischemia - pathology; Brain Ischemia - prevention & control; Caspase 3; Caspases - metabolism; Chronic cerebral hypoperfusion; Cilostazol; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Immunohistochemistry - methods; In Situ Nick-End Labeling - methods; Male; Medical sciences; Neuroglia - drug effects; Neuroglia - pathology; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - administration & dosage; Optic tract; Pharmacology. Drug treatments; Rats; Rats, Wistar; Tetrazoles - administration & dosage; Tumor Necrosis Factor-alpha - metabolism; TUNEL; White matter
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.01.088

In the present study, we elucidated effect of cilostazol to prevent the occurrence of vacuolation and rarefaction of the white matter in association with apoptosis induced by bilateral occlusion of common carotid arteries in the male Wistar rats. Rats orally received vehicle (DMSO) or 60 mg kg −1 day −1 (orally) cilostazol for 3, 7, 14 or 30 days. In the vehicle group, increased vacuolation and rarefactions in the white matter were accompanied by extensive activation of both microglial and astroglial cells with suppression of oligodendrocytes in association with increased TNF-α production, caspase-3 immunoreactivity and TUNEL-positive cells in the white matter including optic tract. Post-treatment with cilostazol (60 mg kg −1 day −1) strongly suppressed not only elevated activation of astroglia and microglia but also diminished oligodendrocytes following chronic cerebral hypoperfusion. In conclusion, cilostazol (60 mg kg −1 day −1, orally) significantly reduced the apoptotic cell death in association with decreased TNF-α production and caspase-3-positive cells in the white matter of rat brains subjected to bilateral occlusion of common carotid arteries, consequently ameliorating vacuoles and rarefaction changes in the white matter.