Neuroprotection by cilostazol, a phosphodiesterase type 3 inhibitor, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion.
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-alpha 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-alpha 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.
Lee
Jeong Hyun
JH
Department of Pharmacology, College of Medicine, Pusan National University, 10 Ami-Dong 1-Ga, Seo-Gu, Busan 602-739, Korea.
Park
So Youn
SY
Shin
Yung Woo
YW
Hong
Ki Whan
KW
Kim
Chi Dae
CD
Sung
Sang-Min
SM
Kim
Ki Young
KY
Lee
Won Suk
WS
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D000077407:Cilostazol; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018696:Neuroprotective Agents; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000077407:Cilostazol