Table 1.
In vivo effects of cilostazol on animal models of cerebral ischemia and chronic cerebral hypoperfusion.
| Animal model | Dose of cilostazol | Effects | Reference |
|---|---|---|---|
| Transient MCAO in rat | 10 mg/kg, i.v. (5 min or 1 h after ischemia) | Increased the cAMP, Bcl‐2 and decreased the TNF‐α, Bax scavenged hydroxyl, and peroxyl radicals | Choi et al. 2002 |
| Transient MCAO in rat | 30 mg/kg, p.o. (5 min, 4 h after ischemia) | Reduced the ischemic edema (MRI study) | Lee et al. 2003 |
| Transient MCAO in rat | 30 mg/kg, p.o. (5 min, 4 h after ischemia) | Increased the CREB, Akt phosphorylation, and the Bcl‐2 | Lee et al. 2004 |
| Transient MCAO in rat | 30 mg/kg, p.o. (5 min, 4 h after ischemia) | PARP inhibition, decreased the TUNEL, microglia, TNF‐α positive cells, and AIF translocation | Lee et al. 2007 |
| Transient MCAO in mice | 3–10 mg/kg, i.p. (30 min before MCAO) | Attenuated ischemic neuronal injury and inhibited blood–brain barrier disruption | Ye et al. 2007 |
| 10 mg/kg, i.p. (1, 2, and 3 h after ischemia) | Inhibited astrocyte proliferation/glial scar formation | ||
| 10 mg/kg, i.p. (1, 4, and 7 h after ischemia) | Accelerated the angiogenesis | ||
| Permanent MCAO in rat | 30 or 50 mg/kg, p.o. (30 min, 4 h after MCAO) | Reduced the gray and white matter damage; improved the CBV and CBF in the peri‐infarct area; increased perfusion in the ischemic penumbra | Honda et al. 2006 |
| Permanent MCAO in mice | 30 mg/kg, i.p. (12 h, 1 h before and after MCAO) | Increased metallothionein‐1 and ‐2 in penumbra | Wakida et al. 2006 |
| BCCAL in rat | 50 mg/kg/day, p.o. | Protected against cerebral hypoperfusion‐induced cognitive impairment and white matter damage; increased p‐CREB, Bcl‐2, and COX‐2 | Watanabe et al. 2006 |
| BCCAL in rat | 60 mg/kg/day, p.o. | Suppressed the activation of microglia and astrocytes but also diminished oligodendrocyte; decreased TNF‐α and apoptosis in white matter lesion | Lee et al. 2006 |
MCAO = middle cerebral artery occlusion; BCCAL = bilateral common carotid artery ligation; CREB = cAMP‐response element binding protein; CBF = cerebral blood flow; CBV = cerebral blood volume; i.v. = intravenous; i.p. = intraperitoneal; p.o. = peroral.