Cilostazol attenuates gray and white matter damage in a rodent model of focal cerebral ischemia.
OBJECTIVE
To evaluate whether delayed treatment with the antiplatelet agent cilostazol reduces the volume of infarction in the gray and white matter in a rodent model of permanent focal cerebral ischemia and to explore the mechanism of the neuroprotective effect in vivo.


METHODS
Cilostazol (30 or 50 mg/kg) or vehicle was administered by gavage 30 minutes and 4 hours after the induction of cerebral ischemia by permanent occlusion of the left middle cerebral artery (MCA). Animals were euthanized 24 hours after MCA occlusion, and the volume of gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein immunohistochemistry. Dynamic susceptibility contrast MRI was used to assess regional cerebral blood volume (CBV) and cerebral blood flow (CBF).


RESULTS
Treatment with the higher dose of cilostazol (50 mg/kg) significantly reduced the volume of gray matter damage and axonal damage in the cerebral hemisphere by 45.0% (P<0.02) and 42.4% (P<0.002), respectively, compared with the control group. Relative CBV in the peri-infarct area after MCA occlusion was significantly increased in the cilostazol-treated group (50 mg/kg) compared with the control group (P<0.05). Relative CBF tended to be higher in the cilostazol-treated group compared with the control group.


CONCLUSIONS
Treatment with cilostazol significantly reduced the gray and white matter damage associated with permanent focal ischemia. Cilostazol improved CBV and CBF in the peri-infarct area. The major action of cilostazol is to increase perfusion in the ischemic penumbra.
Honda
Fumiaki
F
Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Imai
Hideaki
H
Ishikawa
Makoto
M
Kubota
Chisato
C
Shimizu
Tatsuya
T
Fukunaga
Mari
M
Saito
Nobuhito
N
D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D000077407:Cilostazol; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D015233:Models, Statistical; D018696:Neuroprotective Agents / Q000494:pharmacology; D010477:Perfusion; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D018696:Neuroprotective Agents; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol