The time window in which a drug is effective varies between drugs. The present study investigated the therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion in mice. Animals underwent midd...The time window in which a drug is effective varies between drugs. The present study investigated the therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion in mice. Animals underwent middle cerebral artery occlusion and were injected with Qingkailing （1.5, 3, 6 mL/kg）. Infarct volume and neurological function were assessed after 24 hours of ischemia. In addition, to establish the therapeutic time window, mice were injected with 3 mL/kg Qingkailing at 0, 1, 3, 4, 6, 9 and 12 hours after occlusion. Results revealed that Qingkailing injection significantly reduced infarct volume and improved neurological function in model mice after cerebral infarction for up to 9 hours, demonstrating that the therapeutic window of Qingkailing injection can extend to 9 hours for cerebral ischemia/reperfusion in mice.展开更多
The paper aims to optimize the therapeutic dose and time window of picroside II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery...The paper aims to optimize the therapeutic dose and time window of picroside II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitonenally at different ischemic time with different dose. The concentrations of neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic protein (MBP) in serum were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The results indicated that best therapeutic time window and dose of picroside II in cerebral ischemic injury were ischemia 1.5 h with 20 mg/kg body weight according to the concentrations of NSE, S100B and MBP in serum. It is concluded that according to the principle of lowest therapeutic dose with longest time window, the optimized therapeutic dose and time window are injecting picroside II intraperitonenally with 20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats.展开更多
The aim is to optimize the anti-inflammatory effect and the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bi...The aim is to optimize the anti-inflammatory effect and the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods in 30 Wistar rats. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different dose. The concentrations of aquaporins 4 (AQP4), matrix metalloproteinases9 (MMP9) and cyclooxygenase 2 (COX2) in serum and brain tissue were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The best therapeutic time window and dose of picroside II in cerebral ischemic injury were 1) ischemia 2.0 h with 20 mg/kg and 1.5 h with 20 mg/kg body weight according to the concentration of AQP4 in serum and brain tissue;2) ischemia 1.5 h with 20 mg/kg and ischemia 2.0 h with 20 mg/kg according to the concentrations of MMP9 in serum and brain tissue;and 3) ischemia 1.5 h with 10 mg/kg and ischemia 1.5 h with 20 mg/kg according to the concentrations of COX2 in serum and brain tissue respectively. According to the principle of the lowest therapeutic dose with the longest time window, the optimized therapeutic dose and time window were injecting picroside II intraperitoneally with 10 - 20 mg/kg body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury.展开更多
A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. ...A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside Ⅱ inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows： （1） 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; （2） 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; （3） 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and （4） 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit.展开更多
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 ...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.展开更多
BACKGROUND： Aquaporin-4 （AQP-4） over-expression following cerebral ischemia results in cerebral edema. Picroside Ⅱ has been shown to exhibit a neuroprotective effect on neuronal apoptosis. However, few reports hav...BACKGROUND： Aquaporin-4 （AQP-4） over-expression following cerebral ischemia results in cerebral edema. Picroside Ⅱ has been shown to exhibit a neuroprotective effect on neuronal apoptosis. However, few reports have addressed the neuroprotective mechanisms and therapeutic times following cerebral ischemic reperfusion injury. OBJECTIVE： To explore the neuroprotective effects and ideal treatment window for picroside Ⅱ treatment of middle cerebral artery occlusion and reperfusion injury in rats. DESIGN, TIME AND SETTING; A randomized, controlled, animal experiment was performed at Institute of Cerebrovascular Diseases, Qingdao University Medical College from September 2008 to May 2009. MATERIALS： Picroside II was purchased from Tianjin Kuiqing Medical Technology, China. METHODS： A total of 165 adult, healthy, male, Wistar rats were randomly assigned to sham-surgery （n = 15）, model （n = 75）, and treatment groups （n = 75）. Rats in the model and treatment groups underwent middle cerebral artery occlusion and reperfusion through the use of an intraluminal monofilament suture on the left external-internal carotid artery, The treatment group was injected with 1.0% picroside Ⅱ （10 mg/kg） into the tail vein, and the model and sham-surgery groups were injected with 0.1 mol/L phosphate buffered saline （250 μL）. MAIN OUTCOME MEASURES： Neurological functional scores were evaluated using the Longa＇s method; cerebral infarction volume was detected through the use of tetrazolium chlodde staining; cellular apoptosis was determined through the use of the in situ end-labeling method; aquaporin-4 expression was measured using fluorescence labeling analysis and reverse transcription polymerase chain reaction technique. RESULTS： At 0.5 hour following cerebral ischemic injury, neurological functional scores were low, and a small infarction focus was detected in the ischemic cortex of the model group. Along with prolonged ischemia and an increased number of apoptosis-positive cells, AQP-4 mRNA and protein expression was increased. At 1-2 hours after ischemia, neurological scores and infarction sizes were significantly increased in the model group. Apoptotic-positive cells were widespread in the ipsilateral cortex and stdatum. In addition, AQP-4 mRNA and protein expression levels were increased. Picroside II treatment significantly decreased neurological scores and infarction volume, and reduced AQP-4 mRNA and protein expression levels compared with the model group （P 〈 0.05 or P 〈 0.01）. At 1 hour after ischemia, the therapeutic effect of picroside Ⅱ was notable （P 〈 0.01）. CONCLUSION： Picroside Ⅱ played a protective role in cerebral ischemic reperfusion injury by inhibiting apoptosis and regulating AQP-4 expression. The best therapeutic time window was 1 hour after cerebral ischemic reperfusion.展开更多
We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immed...We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI（3 mg/kg） through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa＇s method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy. The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling（TUNEL） assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following： Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.展开更多
Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. Thi...Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil （FA, COX inhibitor） and its therapeutic time window in a model of transient middle cerebral artery occlusion （MCAO） in rats. Methods Forty-eight male SD rats were randomly assigned into six groups （n=8 in each group）; three FA groups, vehicle, sham and ischemia/reperfusion （I/R） groups. Three doses of FA （5, 10 or 20 mg/kg, intravenous infusion） were administered just after cerebral ischemia/reperfusion （I/R）. The degree of neurological outcome was measured by the neurologic deficit score （NDS） at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） staining at 72 hours after I/R. In three other groups （n=8 in each group）, the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.展开更多
基金the Science and Technology Major Projects for Major New Drugs, No.2009ZX09102-136
文摘The time window in which a drug is effective varies between drugs. The present study investigated the therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion in mice. Animals underwent middle cerebral artery occlusion and were injected with Qingkailing （1.5, 3, 6 mL/kg）. Infarct volume and neurological function were assessed after 24 hours of ischemia. In addition, to establish the therapeutic time window, mice were injected with 3 mL/kg Qingkailing at 0, 1, 3, 4, 6, 9 and 12 hours after occlusion. Results revealed that Qingkailing injection significantly reduced infarct volume and improved neurological function in model mice after cerebral infarction for up to 9 hours, demonstrating that the therapeutic window of Qingkailing injection can extend to 9 hours for cerebral ischemia/reperfusion in mice.
文摘The paper aims to optimize the therapeutic dose and time window of picroside II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitonenally at different ischemic time with different dose. The concentrations of neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic protein (MBP) in serum were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The results indicated that best therapeutic time window and dose of picroside II in cerebral ischemic injury were ischemia 1.5 h with 20 mg/kg body weight according to the concentrations of NSE, S100B and MBP in serum. It is concluded that according to the principle of lowest therapeutic dose with longest time window, the optimized therapeutic dose and time window are injecting picroside II intraperitonenally with 20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats.
文摘The aim is to optimize the anti-inflammatory effect and the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods in 30 Wistar rats. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different dose. The concentrations of aquaporins 4 (AQP4), matrix metalloproteinases9 (MMP9) and cyclooxygenase 2 (COX2) in serum and brain tissue were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The best therapeutic time window and dose of picroside II in cerebral ischemic injury were 1) ischemia 2.0 h with 20 mg/kg and 1.5 h with 20 mg/kg body weight according to the concentration of AQP4 in serum and brain tissue;2) ischemia 1.5 h with 20 mg/kg and ischemia 2.0 h with 20 mg/kg according to the concentrations of MMP9 in serum and brain tissue;and 3) ischemia 1.5 h with 10 mg/kg and ischemia 1.5 h with 20 mg/kg according to the concentrations of COX2 in serum and brain tissue respectively. According to the principle of the lowest therapeutic dose with the longest time window, the optimized therapeutic dose and time window were injecting picroside II intraperitoneally with 10 - 20 mg/kg body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury.
基金supported by the National Natural Science Foundation of China,No.81041092,81274116
文摘A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside Ⅱ inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows： （1） 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; （2） 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; （3） 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and （4） 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit.
文摘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.
基金the National Natural Science Foundation of China,No. 30873391
文摘BACKGROUND： Aquaporin-4 （AQP-4） over-expression following cerebral ischemia results in cerebral edema. Picroside Ⅱ has been shown to exhibit a neuroprotective effect on neuronal apoptosis. However, few reports have addressed the neuroprotective mechanisms and therapeutic times following cerebral ischemic reperfusion injury. OBJECTIVE： To explore the neuroprotective effects and ideal treatment window for picroside Ⅱ treatment of middle cerebral artery occlusion and reperfusion injury in rats. DESIGN, TIME AND SETTING; A randomized, controlled, animal experiment was performed at Institute of Cerebrovascular Diseases, Qingdao University Medical College from September 2008 to May 2009. MATERIALS： Picroside II was purchased from Tianjin Kuiqing Medical Technology, China. METHODS： A total of 165 adult, healthy, male, Wistar rats were randomly assigned to sham-surgery （n = 15）, model （n = 75）, and treatment groups （n = 75）. Rats in the model and treatment groups underwent middle cerebral artery occlusion and reperfusion through the use of an intraluminal monofilament suture on the left external-internal carotid artery, The treatment group was injected with 1.0% picroside Ⅱ （10 mg/kg） into the tail vein, and the model and sham-surgery groups were injected with 0.1 mol/L phosphate buffered saline （250 μL）. MAIN OUTCOME MEASURES： Neurological functional scores were evaluated using the Longa＇s method; cerebral infarction volume was detected through the use of tetrazolium chlodde staining; cellular apoptosis was determined through the use of the in situ end-labeling method; aquaporin-4 expression was measured using fluorescence labeling analysis and reverse transcription polymerase chain reaction technique. RESULTS： At 0.5 hour following cerebral ischemic injury, neurological functional scores were low, and a small infarction focus was detected in the ischemic cortex of the model group. Along with prolonged ischemia and an increased number of apoptosis-positive cells, AQP-4 mRNA and protein expression was increased. At 1-2 hours after ischemia, neurological scores and infarction sizes were significantly increased in the model group. Apoptotic-positive cells were widespread in the ipsilateral cortex and stdatum. In addition, AQP-4 mRNA and protein expression levels were increased. Picroside II treatment significantly decreased neurological scores and infarction volume, and reduced AQP-4 mRNA and protein expression levels compared with the model group （P 〈 0.05 or P 〈 0.01）. At 1 hour after ischemia, the therapeutic effect of picroside Ⅱ was notable （P 〈 0.01）. CONCLUSION： Picroside Ⅱ played a protective role in cerebral ischemic reperfusion injury by inhibiting apoptosis and regulating AQP-4 expression. The best therapeutic time window was 1 hour after cerebral ischemic reperfusion.
基金supported by the National Natural Science Foundation of China,No.81571114 and 81771267(to ZH)the National Science Funds for Distinguished Youth Scholars of China,No.81325007(to XMJ)+2 种基金the Distinguished Professor of Cheung Kong Scholars Program in China,No.T2014251(to XMJ)the Wenzhou Municipal Sci-Tec Bureau Programs in China,No.Y20120154(to ZZ) and Y20140686(to ZH)the Projects of International Cooperation and Exchanges National Natural Science Foundation of China,No.81620108011(to XMJ)
文摘We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI（3 mg/kg） through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa＇s method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy. The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling（TUNEL） assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following： Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.
基金This study was supported by a grant from the National Nature Science Foundation of China （No. 30872445）.
文摘Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil （FA, COX inhibitor） and its therapeutic time window in a model of transient middle cerebral artery occlusion （MCAO） in rats. Methods Forty-eight male SD rats were randomly assigned into six groups （n=8 in each group）; three FA groups, vehicle, sham and ischemia/reperfusion （I/R） groups. Three doses of FA （5, 10 or 20 mg/kg, intravenous infusion） were administered just after cerebral ischemia/reperfusion （I/R）. The degree of neurological outcome was measured by the neurologic deficit score （NDS） at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） staining at 72 hours after I/R. In three other groups （n=8 in each group）, the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.
