Abstract
Objective: To study the neuroprotective effect of picrosede II and explore the best therapeutic dose and time window according to orthogonal design in cerebral ischemic injury in rats. Methods: The forebrain ischemia rat models were established by bilateral common carotid artery occlusion (BCCAO) method. The successful models were randomly grouped according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different doses. The contents of neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic protein (MBP) in serum and brain tissue were determined by enzyme linked immunosorbent assay (ELISA) to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. Results: The best therapeutic time window and dose of picroside II in cerebral ischemic injury may be 1) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg body weight according to the content of NSE in serum and brain tissue respectively, 2) ischemia 1.5 h with 20 mg/kg according to the content of S100B in both serum and brain tissue, and 3) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg according to the content of MBP in serum and brain tissue respectively. Conclusion: Based on the principle of the minimization of therapeutic drug dose and maximization of therapeutic time window, the optimal composition of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury should be achieved by injecting picroside II intraperitoneally with 10-20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats.
Highlights
Neuronspecific enolase (NSE) occupies 40% - 65% of enolase in the cortex [1] and exists in neurons and neural endocrine cells to form the membrane structure and repair nerve cell [2]
The best therapeutic time window and dose of picroside II in cerebral ischemic injury may be 1) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg body weight according to the content of NSE in serum and brain tissue respectively, 2) ischemia 1.5 h with 20 mg/kg according to the content of S100B in both serum and brain tissue, and 3) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg according to the content of Myelin basic protein (MBP) in serum and brain tissue respectively
Based on the principle of the minimization of therapeutic drug dose and maximization of therapeutic time window, the optimal composition of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury should be achieved by injecting picroside II intraperitoneally with 10 - 20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats
Summary
Neuronspecific enolase (NSE) occupies 40% - 65% of enolase in the cortex [1] and exists in neurons and neural endocrine cells to form the membrane structure and repair nerve cell [2]. Clinical trials indicated that Shuxuetong injection, a kind of traditional Chinese medicine, could significantly reduce the serum NSE level and protect effectively the brain injury [6]. All of those proved that NSE could be used as an objective index to judge the extent of cerebral ischemic damage and prognosis [7,8,9]. Clinical trials showed that the concentration of serum S100B increased significantly in ischemic stroke patients [12], and related closely to the classification, serious degree, infarct volume and mortality of ischemic stroke [13]. Myelin basic protein (MBP) locates in the serous membrane surface of myelin sheath and combines closely to myelin sheath lipid, which is JBBS
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