In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion in...In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/ reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulated, the oxidative stress-related marker malondialdehyde was increased, and super- oxide dismutase activity was decreased in the ischemic cerebral cortex. Atorvastatin pretreatment significantly inhibited these changes. Our findings indicate that atorvastatin protects against ce-rebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects.展开更多
BACKGROUND： Patients with type-2 diabetes mellitus exhibit higher levels of plasma endothelin-1 （ET-1）. However, very few reports exist regarding altered endothelin-3 （ET-3） and ET-1 concentrations in brain tissu...BACKGROUND： Patients with type-2 diabetes mellitus exhibit higher levels of plasma endothelin-1 （ET-1）. However, very few reports exist regarding altered endothelin-3 （ET-3） and ET-1 concentrations in brain tissue. OBJECTIVE： To observe expression changes of ET-3 and glial fibrillary acidic protein （GFAP） in the frontal and parietal cortex of type-2 diabetic mice following ischemia-reperfusion injury, with various reperfusion durations. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was conducted in the Xiangya Medical College of Central South University and the Third Xiangya Hospital between February 2002 and January 2003. MATERIALS： Sixty-six, adult, male, Kunming mice, weighing （30 ± 5） g, as well as rabbit anti-ET-3 polyclonal and rabbit anti-GFAP polyclonal antibodies, were provided by the Neurobiology Institute of Second Military Medical University in Japan. METHODS： Sixty-six mice were randomly divided into five groups： diabetes mellitus （DM, n = 6）, diabetes mellitus with ischemia-reperfusion （DM/IR, n = 24）, ischemia-reperfusion （IR, n = 24）, sham operation （SO, n = 6）, and control （n = 6）. MAIN OUTCOME MEASURES： Following ischemia-reperfusion for 1, 3, 5, and 10 days, respectively, expression of ET- 3 and GFAP was immunohistochemically measured in the frontal and parietal cortex. RESULTS： All 66 mice were included in the final result analysis. In the IR and DM/IR groups, ET-3- and GFAP-positive neurons increased in the frontal and parietal cortex in response to one day reperfusion, peaked at five days, and decreased at 10 days. ET-3 and GFAP expression was significantly greater in the DM/IR group after reperfusion for 1 day compared to the IR group. However, at other time points, there were no significant differences between the two groups. CONCLUSION： Brain ischemia-reperfusion injury results in overexpression of ET-3 and activation of astrocytes. Diabetes increases the number of ET-3- and GFAP-positive astrocytes in brain tissue of ischemia-reperfusion mice with the same reperfusion duration.展开更多
BACKGROUND： Clinical practice and modern pharmacology have confirmed that chlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE： To observe the effects of chlorogenic acid on neuronal nitric oxi...BACKGROUND： Clinical practice and modern pharmacology have confirmed that chlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE： To observe the effects of chlorogenic acid on neuronal nitric oxide synthase （nNOS）-positive neurons in the mouse hippocampus, and to investigate the mechanisms underlying the beneficial effects of chlorogenic acid on learning and memory. DESIGN, TIME AND SETTING： The present randomized, controlled, neural cell morphological observation was performed at the Institute of Neurobiology, Central South University between January and May 2005. MATERIALS： Forty-eight female, healthy, adult, Kunming mice were included in this study. Learning and memory impairment was induced with an injection of 0.5 uL kainic acid （0.4 mg/mL） into the hippocampus. METHODS： The mice were randomized into three groups （n = 16）： model, control, and chlorogenic acid-treated. At 2 days following learning and memory impairment induction, intragastric administration of physiological saline or chlorogenic acid was performed in the model and chlorogenic acid-treated groups, respectively. The control mice were administered 0.5uL physiological saline into the hippocampus, and 2 days later, they received an intragastfic administration of physiological saline. Each mouse received two intragastric administrations （1 mL solution once） per day, for a total of 35 days. MAIN OUTCOME MEASURES： Detection of changes in hippocampal and cerebral cortical nNOS neurons by immunohistochemistry; determination of spatial learning and memory utilizing the Y-maze device. RESULTS： At day 7 and 35 after intervention, there was no significant difference in the number of nNOS-positive neurons in the cerebral cortex between the model, chlorogenic acid, and control groups （P 〉 0.05）. Compared with the control group, the number of nNOS-positive neurons in the hippocampal CA1-4 region was significantly less in the model group （P 〈 0.05）. However, the control group was not different from the chlorogenic acid-treated group （P 〉 0.05）. At day 7 following intervention, the number of correct responses in the Y-maze test was greater in the chlorogenic acid-treated group than in the model group. CONCLUSION： Chlorogenic acid protects kainic acid-induced injury to nNOS-positive neurons in the hippocampal CA1-4 regions, thereby ameliorating learning and memory impairment.展开更多
基金the Natural Science Foundation of Hunan Province in China,No.11JJ5081grants from Hunan Provincial Science and Technology Department in China,No.2012SK3226 and 2011SK3236the National Natural Science Foudation of China,No.81271298/H0906
文摘In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/ reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulated, the oxidative stress-related marker malondialdehyde was increased, and super- oxide dismutase activity was decreased in the ischemic cerebral cortex. Atorvastatin pretreatment significantly inhibited these changes. Our findings indicate that atorvastatin protects against ce-rebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects.
文摘BACKGROUND： Patients with type-2 diabetes mellitus exhibit higher levels of plasma endothelin-1 （ET-1）. However, very few reports exist regarding altered endothelin-3 （ET-3） and ET-1 concentrations in brain tissue. OBJECTIVE： To observe expression changes of ET-3 and glial fibrillary acidic protein （GFAP） in the frontal and parietal cortex of type-2 diabetic mice following ischemia-reperfusion injury, with various reperfusion durations. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was conducted in the Xiangya Medical College of Central South University and the Third Xiangya Hospital between February 2002 and January 2003. MATERIALS： Sixty-six, adult, male, Kunming mice, weighing （30 ± 5） g, as well as rabbit anti-ET-3 polyclonal and rabbit anti-GFAP polyclonal antibodies, were provided by the Neurobiology Institute of Second Military Medical University in Japan. METHODS： Sixty-six mice were randomly divided into five groups： diabetes mellitus （DM, n = 6）, diabetes mellitus with ischemia-reperfusion （DM/IR, n = 24）, ischemia-reperfusion （IR, n = 24）, sham operation （SO, n = 6）, and control （n = 6）. MAIN OUTCOME MEASURES： Following ischemia-reperfusion for 1, 3, 5, and 10 days, respectively, expression of ET- 3 and GFAP was immunohistochemically measured in the frontal and parietal cortex. RESULTS： All 66 mice were included in the final result analysis. In the IR and DM/IR groups, ET-3- and GFAP-positive neurons increased in the frontal and parietal cortex in response to one day reperfusion, peaked at five days, and decreased at 10 days. ET-3 and GFAP expression was significantly greater in the DM/IR group after reperfusion for 1 day compared to the IR group. However, at other time points, there were no significant differences between the two groups. CONCLUSION： Brain ischemia-reperfusion injury results in overexpression of ET-3 and activation of astrocytes. Diabetes increases the number of ET-3- and GFAP-positive astrocytes in brain tissue of ischemia-reperfusion mice with the same reperfusion duration.
文摘BACKGROUND： Clinical practice and modern pharmacology have confirmed that chlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE： To observe the effects of chlorogenic acid on neuronal nitric oxide synthase （nNOS）-positive neurons in the mouse hippocampus, and to investigate the mechanisms underlying the beneficial effects of chlorogenic acid on learning and memory. DESIGN, TIME AND SETTING： The present randomized, controlled, neural cell morphological observation was performed at the Institute of Neurobiology, Central South University between January and May 2005. MATERIALS： Forty-eight female, healthy, adult, Kunming mice were included in this study. Learning and memory impairment was induced with an injection of 0.5 uL kainic acid （0.4 mg/mL） into the hippocampus. METHODS： The mice were randomized into three groups （n = 16）： model, control, and chlorogenic acid-treated. At 2 days following learning and memory impairment induction, intragastric administration of physiological saline or chlorogenic acid was performed in the model and chlorogenic acid-treated groups, respectively. The control mice were administered 0.5uL physiological saline into the hippocampus, and 2 days later, they received an intragastfic administration of physiological saline. Each mouse received two intragastric administrations （1 mL solution once） per day, for a total of 35 days. MAIN OUTCOME MEASURES： Detection of changes in hippocampal and cerebral cortical nNOS neurons by immunohistochemistry; determination of spatial learning and memory utilizing the Y-maze device. RESULTS： At day 7 and 35 after intervention, there was no significant difference in the number of nNOS-positive neurons in the cerebral cortex between the model, chlorogenic acid, and control groups （P 〉 0.05）. Compared with the control group, the number of nNOS-positive neurons in the hippocampal CA1-4 region was significantly less in the model group （P 〈 0.05）. However, the control group was not different from the chlorogenic acid-treated group （P 〉 0.05）. At day 7 following intervention, the number of correct responses in the Y-maze test was greater in the chlorogenic acid-treated group than in the model group. CONCLUSION： Chlorogenic acid protects kainic acid-induced injury to nNOS-positive neurons in the hippocampal CA1-4 regions, thereby ameliorating learning and memory impairment.
