The Neuroprotective Effects Of BPI-1095 In Focal Cerebral Ischemia Rats

Objective: Aspirin-acetylsalicylic acid (ASA) is widelyused anti-platelet aggregation agent and it is able to preventattack of acute cerebral ischemia. However, clinical usage hasbeen limited as a result of adverse effects on alimentary tract andrenal system. NO-releasing ASA(NO-ASA) such as NCX-4215and NCX-4016 are similarly derived from ASA and have beenshown to demonstrate antithrombotic effect without ASA sideeffects on gastric mucosa. BPI-1095 which is derived fromNO-ASAs is still under preclinical study phase. The studyinvestigated the effect of different doses of BPI-1095 on infarctsize and neurological outcome and apoptotic related proteinexpression in MCAo rats.Methods : Cerebral ischemia was induced by middlecerebral artery occlusion (MCAo) in adult male SD rats. ratswere randomly dicided into six groups of fifteen. Each rat hasbeen given different dosage tested medication and was sacrificed24 h after treatment. Neurologic functional behaviour tests wereperformed at 4 h and 24 h to evaluate neurologic deficits fromdifferent aspects.After the final behaviour test, 7 or 8 rats (remain 5 rats forbrain tissue stain) were picked up randomly from the successfullymade models among each group. The brain was removed fromthe skull, cut into 6 coronal blocks, each with 2-mm thickness,and stained by 2% triphenyl–tetrazolium chloride (TTC). Thesize of infarction was measured on each slice by image analysissystem. The contralateral and ipsilateral hemisphere areas weremeasured. The percentage of hemisphere suffering infarction wasthen calculated as the instruction of Swanson's formula.After the final behavior test, 5 rats from each group werekilled and brains were removed and frozen by liquid nitrogen;40μm-thick sections were taken with a cryotome. Thepathological characters were observed by HE stain. Meanwhile,immunohistochemistry staining was used to identify Bcl-2,Caspase-3 expression in ischemic brain tissue and percentage ofpositive cells were calculated by image analysis system.All data were expressed as mean ±SE. Neurologicalbehaviour tests scores and the percentages of infarct area andpositive cells were evaluated by a one-way ANOVA and followedby the Student–Newman–Keul test. P<0.05 demonstratedsignificant difference among groups.Results: 1.BPI-1095 effectively improved the neurologicaldeficit. Remarkable recovery of neurological function wasdetected in rats treated with moderate (80 mg/kg) or big (240mg/kg) doses at 24 h after treatment (p<0.05, vs vehicle-treatedgroup).2.The percentage of infarcted area were significantlydecreased in big and moderate dose treated rats (P<0.05, vs the...