Table 4.
Targeting Gi-coupled prostanoid receptors for experimental brain ischemia.
| Receptor | Animal model | Major therapeutic outcomes | Reference |
|---|---|---|---|
| DP2 | Hypoxic ischemia (30 min) induced in BALB/cAJcl neonatal mice (P7) | The ischemic lesion in cerebral cortex and basal ganlia was not changed in DP2 knock-out mice 24 hr after hypoxic ischemia. | Taniguchi et al., 2007 |
| EP3 | Transient MCAO (90 min) induced in adult male C57BL/6 mice | Treatment with EP3 agonist ONO-AE-248 (0.5, 2.5, and 5.0 nmol, i.c.v.) 50-60 min before MCAO exacerbated the infarct volume in a dose-dependent manner 4 days after MCAO, but did not affect core body temperature, cerebral blood flow, or mean arterial blood pressure. | Ahmad et al., 2007 |
| Transient MCAO (90 min) induced in adult male C57BL/6 mice | Genetic deletion of the EP3 receptor did not change the infarct volume or cerebral blood flow 24 hr after MCAO. | Li et al., 2008 | |
| Transient MCAO (90 min) induced in adult male C57BL/6 mice | EP3 deficiency decreased the infarct volume and neurological deficit 2 days but not 4 days after MCAO without affecting the mean arterial blood pressure, pH, blood gases (CO2 and O2), cerebral blood flow, or body temperature. | Saleem et al., 2009 | |
| Transient MCAO (120 min) induced in adult male and female C57BL/6 mice | Genetic deletion of mPGES-1 diminished the infarct volume, edema, and neurological deficit 24 hr after MCAO; treatment with EP3 selective antagonist ONO-AE3-240 (3 mg/kg, i.p., 3 doses at 2, 8, and 14 hr after MCAO) reduced infarct volume, edema, and neurological deficit 24 hr after MCAO in wild-type but not in mPGES-1 knockout mice. | Ikeda-Matsuo et al., 2010 | |
| Transient MCAO (120 min) induced in adult male and female C57BL/6 mice | EP3 deficiency or treatment with ONO-AE3-240 (1 or 3 mg/kg, i.p., 3 doses at 2, 8, and 14 hr after MCAO) decreased the infarct volume, edema, neurological deficit, neuronal apoptosis, and blood-brain barrier breakdown, preserved the tight junction proteins, and attenuated the microglial activation 24 hr after MCAO without affecting the cerebral blood flow, mean arterial blood pressure, rectal temperature, or brain vasculature. | Ikeda-Matsuo et al., 2011 |