Protective Effects Of Blipam On Cerebral Ischemia Injury And Mechanism

Blipam is a new type antagonist of intracellular Ca²⁺ and has significant protection on cerebral ischemia. The protective effects and mechanism of Blipam on cerebral ischemic injury were studied on multiple animal models of in the paper. The major experimental results as follow:1. Blipam (6,3 and 1.5mg·kg^-1.iv) prolonged the gasping time of beheaded mice significantly and dose-dependently.2. Blipam (6,3 and 1.5mg·kg^-1.iv) prolonged the survival time of anoxic mice in nitrogen gas and increased the surviving rate after ligating bilateral common carotid artery (CCA) in mice.3. On rat middle cerebral artery occlusion(MCAO) model, Blipam iv 4.8,2.4,1.2 mg·kg^-1 significantly decreased the percentage of cerebral infarction weight, and significantly improved abnormal neurologic symptom.4. The inhibitory effect of Blipam 4.8mg·kg^-1 iv on the percentage of rat cerebral infarction weight last 72h. The protective effects were observed after iv administrating of blipam in rat MCAO 0.5,1.0 and 1.5h, especially, and the effect was the most obvious when blipam was administered at MCAO 0.5h.5. On MCAO model, Blipam iv 4.8,2.4,1.2mg·kg^-1can significantly inhibit the decreases of lactate dehydrogenase(LDH) activity, and reduce the contents of MDA in rat cerebrum. 4.8,2.4 mg.kg^-1 blipam can significantly inhibit the decreases of the content of nitric oxide(NO) in rat cerebrum.6. On the acute incomplete cerebral ischemia model in rat, blipam iv 4.8,2.4,1.2mg·kg^-1 obviously reduced the edema of brain, 4.8, 2.4 mg.kg^-1 blipam significantly reduced the increment of cerebral vasopermeability.7. Blipam iv 0.050,0.025,0.0125mg·ml^-1 significantly inhibited the thrombocytic aggregation indueed by collagen.8. On the CCA-Vein bypass model, Blipam (iv) 4.8,2.4 mg·kg^-1 significantly reduced the wet weight of thrombus in rat.9. Blipam iv 2.0,1.0mg·kg^-1 relaxed dog cervical internai carotid artery(CICA) and vertebral artery and increased the blood flow of brain tissue.Conclusion: Blipam has a significant protection on cerebral ischemia injury via increasing the blood flow of brain tissue, attenuating the cerebral free radical, inhibiting the thrombocytic aggregation and the formation of thrombus.