Table 3.
Targeting Gq-coupled prostanoid receptors for experimental brain ischemia.
| Receptor | Animal model | Major therapeutic outcomes | Reference |
|---|---|---|---|
| EP1 | Transient MCAO (20 min) induced in adult male C57BL/6 mice | Genetic ablation of the EP1 receptor or treatment with EP1 selective antagonist SC51089 (10 μg/kg, i.p., twice per day) beginning at 5 min or 6 hr after ischemia attenuated the infarct volume, neurological deficit, and brain swelling 3 days after MCAO without affecting cerebral blood flow. | Kawano et al., 2006 |
| Transient MCAO (90 min) induced in adult male C57BL/6 mice | EP1 deficiency reduced infarct volume 4 days after MCAO without affecting the post-stroke weight loss. | Ahmad et al., 2006 | |
| Transient MCAO (90 min) induced in adult male C57BL/6 mice | EP1 deficiency decreased the arterial partial pressure of oxygen level during the ischemic stage and improved the ipsilateral cerebral blood flow during the reperfusion without affecting the brain vasculature network. | Saleem et al., 2007 | |
| Transient MCAO (90 min) induced in adult male C57BL/6 mice | Treatment with EP1 antagonist ONO-8713 (0.1, 1, or 10 nmol, i.c.v.) immediately before MCAO reduced the infarct volume 4 days after ischemia without affecting cerebral blood flow. | Ahmad et al., 2008 | |
| Transient MCAO (25 min) induced in adult male and female C57BL/6 mice | Female mice had smaller infarcts than male mice 3 days after transient ischemia; treatment with EP1 antagonist SC51089 (5, 10, or 20 μg/kg, i.p., twice per day) beginning at 5 min, 6 hr, or 12 hr, but not 24 hr after reperfusion decreased the infarct volume in male mice 3 days after ischemia; treatment with SC51089 (10 μg/kg, i.p., twice per day) beginning at 5 min after reperfusion reduced the infarct volume by 41% in female mice 3 days after ischemia. | Abe et al., 2009 | |
| Permanent MCAO induced in adult male C57BL/6 mice | SC51089 (10 μg/kg, i.p., twice per day) beginning at 6 hr after MCAO onset reduced the infarct volume by 39% 24 hr after ischemia. | Abe et al., 2009 | |
| Transient MCAO (25 min) induced in adult male C57BL/6 mice | Treatment with SC51089 (10 μg/kg, i.p., twice per day for 3 days) beginning at 6 hr after reperfusion led to long-term reduction (2 weeks after ischemia) in the infarct volume, the atrophy of the ipsilateral hemisphere, and functional deficit. | Abe et al., 2009 | |
| Transient MCAO (60 min) induced in adult male C57BL/6 mice | Genetic deletion of EP1 decreased the infarct volume, blood-brain barrier breakdown, MMP-9/-3 activity, and ICAM-1 expression in the cortex 24 hr after ischemia. | Frankowski et al., 2015 | |
| Transient MCAO (90 min) induced in adult male Wistar rats | Treatment with EP1 antagonist SC51089 (3 mg/kg, i.v.) at 3, 18, and 28 hr after reperfusion reduced infarct volume, decreased the blood-brain barrier permeability, preserved the tight-junction proteins, prevented the hemorrhagic transformation, attenuated the MMP-9/-3 activity, and reduced the MPO and ICAM-1 levels in the cortex 48 hr after ischemia. | Frankowski et al., 2015 | |
| FP | Transient MCAO (90 min) induced in adult male C57BL/6 mice | Genetic ablation of the FP receptor reduced infarct volume and improved neurological dysfunction 4 days after transient ischemia without affecting cerebral blood flow, body temperature, or arterial blood pressure; treatment with FP selective agonist latanoprost (100 μg/kg, p.o., once) 30 min after reperfusion began aggravated neurological dysfunction and brain infarction in wild-type mice 4 days after MCAO but not in FP knock-out mice. | Saleem et al., 2009 |
| Permanent MCAO induced in adult male C57BL/6 mice | Genetic ablation of the FP receptor or treatment with antagonist AL-8810 (1 or 10 mg/kg, i.v., once) immediately after permanent MCAO began reduced neurological dysfunction and infarct volume in a dose-dependent manner 2 days after MCAO began. | Kim et al., 2012 | |
| TP | Spontaneously hypertensive stroke prone rats (SHRSP) | Oral treatment with TP antagonist terutroban (30 mg/kg per day for 6 weeks) improved survival, delayed the appearance of brain damage and proteinuria, and reduced the expression of IL-1β, TGF-β, and MCP-1 without affecting the thromboxane in serum and urine. | Gelosa et al., 2010 |
| Transient MCAO (90 min) induced in adult male ICR mice | The expression of TP receptor was upregulated by ischemia/reperfusion injury for up to 7 days after MCAO; post-treatment with TP selective antagonist SQ29548 (10 μl, 2.6 μmol/ml, i.c.v. twice) immediately after reperfusion and again 24 hr later attenuated the activation of microglia/macrophages, induction of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and iNOS, blood-brain barrier destruction, infarct volume, and neurological deficit 3 days and 7 days after MCAO without affecting the cerebral blood flow. | Yan et al., 2016 |