beraprost and Brain-Ischemia

Topics: Aged; Aspirin; Brain Ischemia; Drug Therapy, Combination; Epoprostenol; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prognosis; Retrospective Studies; Stroke

BACKGROUND To investigate the combination of beraprost sodium (BPS) and aspirin in the treatment of acute ischemic stroke (AIS). MATERIAL AND METHODS 308 patients with acute cerebral infarction were randomly divided into two groups: experimental group (n=154), treated with BPS (40 μg, tid) and aspirin (100 mg, qd); control group (n=154), treated with 100 mg of aspirin, qd). The antiplatelet therapy remained unchangeable until six months after hospital discharge. RESULTS Initially, no significant differences were found between the two groups. After six months, the relapse-free survival rate was similar between the treatment group (98.1%) and the control group (97.4%). One patient died from AIS in the control group. However, glomerular filtration rate was significantly higher; neurological function and functional ability of patients were better in patients treated with BPS plus aspirin (experimental group) than that in aspirin alone group. No significant difference was found in the function of the coagulation system, suggesting that BPS plus aspirin treatment did not increase the risk of bleeding. Serious adverse events did not occur in both groups. Facial flushing (one case) and mild gastrointestinal reaction (one case) were found in the treatment group without influencing treatment. CONCLUSIONS In our trial involving patients with acute cerebral infarction, BPS plus aspirin was not found to be superior to aspirin in reducing the recurrence of cerebral infarction or death. However, BPS plus aspirin treatment could improve renal function and neurological function without increasing the risk of bleeding.

Topics: Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Cerebral Infarction; Drug Therapy, Combination; Epoprostenol; Female; Glomerular Filtration Rate; Humans; Ischemia; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Treatment Outcome

We and others have identified that inhibition of cyclooxygenase might not be the optimal approach to limiting brain damage after stroke. Now we are investigating the unique properties of the various prostaglandin receptors to determine whether blocking those that mediate toxicity or stimulating those that reduce toxicity will improve neurological outcomes. Here, we determined the respective contribution of the prostaglandin I(2) (PGI(2)) receptor in transient middle cerebral artery (MCA) occlusion (tMCAO) and permanent MCAO (pMCAO) preclinical stroke models by using male wildtype (WT) and IP receptor knockout (IP(-/-)) C57Bl/6 mice. In addition, we investigated the putative preventive and therapeutic effects of the IP receptor agonist beraprost. The infarct volumes and neurological deficit scores (NDS) were significantly greater in IP(-/-) than in WT mice after both tMCAO and pMCAO. Interestingly, beraprost pretreatment (50 or 100 microg/kg p.o.) 30 min before tMCAO and post-treatment (100 microg/kg p.o.) at 2 or 4.5 h of reperfusion significantly reduced the neurological deficit score and infarct volume in WT mice. Post-treatment with beraprost (100 microg/kg p.o.) 4.5 h after pMCAO also significantly decreased neurological deficits and infarct volume in WT mice. Together, these novel findings suggest for the first time that PGI(2) IP receptor activation can attenuate anatomical and functional damage following ischemic stroke.

Topics: Animals; Brain Ischemia; Cohort Studies; Epoprostenol; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuroprotective Agents; Receptors, Epoprostenol

We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selectively damaged endothelium in the pial vessels, the middle cerebral artery was occluded in both groups and maintained for 30 minutes. In Group 2, 50 ng/kg/min TRK-100 was continuously infused intravenously following ultraviolet irradiation. In both the pial arteries and veins, platelet aggregate adhesion to the endothelium with subsequent thrombus formation was significantly (p less than 0.01 and p less than 0.05, respectively) inhibited during middle cerebral artery occlusion in Group 2 compared with Group 1. Similarly, blood flow stasis in the pial veins was effectively prevented in Group 2 during occlusion. Furthermore, the pial artery diameter returned to the control level during the late period of occlusion, whereas in Group 1 the pial artery remained constricted. Our data suggest that TRK-100 can prevent microcirculatory derangement in the acute stage of ischemic stroke.

Topics: Animals; Brain; Brain Ischemia; Cats; Endothelium; Epoprostenol; Female; Male; Microcirculation; Platelet Aggregation; Platelet Aggregation Inhibitors