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AIM: To investigate the protective effect of ginsenoside Rb1 on brain through Cav-1 in mice with cerebral ischemia-reperfusion injury. METHODS: One hundred and twenty C57/B6 mice were randomly divided into sham operation group, model group, model + ginsenoside Rb1 group, ginsenoside Rb1+ Cav-1 siRNA group, ginsenoside Rb1+siNC group, 24 in each group. The model of cerebral ischemia-reperfusion injury in mice was established by middle cerebral artery occlusion (MCAO). The ginsenoside Rb1 group received intraperitoneally injection of ginsenoside Rb1 (40 mg/kg); the sham operation group and model group were intraperitoneally injected with an equal amount of physiological saline immediately after modeling. For the ginsenoside Rb1+ cav-1 siRNA group and the ginsenoside Rb1+siNC group, cav-1 siRNA and siNC were injected into the lateral ventricle 24 h before molding, respectively, and the other operations were the same as the ginsenoside Rb1 group. The neurobehavioral scores of the mice in each group were measured at 24 h after reperfusion, and the water content of brain tissue, cerebral infarction volume, Cav-1 mRNA and Cav-1, Bcl-2 and Bax protein expressions in the cerebral cortex penumbra were measured in each group. RESULTS:Compared with the sham operation group, the neurobehavioral scores, cerebral infarction volume and brain tissue water content in the model group were significantly increased (P<0.05), and the expressions of Cav-1 mRNA and Cav-1 protein, and the Bcl-2 /Bax ratio were significantly decreased (P<0.05). Compared with the model group, the neurobehavioral scores, cerebral infarction volume and brain tissue water content in the ginsenoside Rb1 group were significantly decreased, and the expressions of Cav-1 mRNA and Cav-1 protein, and the Bcl-2 /Bax ratio were significantly increased (P<0.05). Compared with the ginsenoside Rb1 group, the neurobehavioral scores, cerebral infarction volume and brain tissue water content in the ginsenoside Rb1 + cav-1 siRNA group were significantly increased, and the expressions of Cav-1 mRNA and Cav-1 protein, and the Bcl-2 /Bax ratio were significantly decreased (P<0.05). CONCLUSION: Ginsenoside Rb1 can protects brain for mice with cerebral ischemia-reperfusion injury. After Cav-1 siRNA decreased the expression of Cav-1 protein in the brain tissue of mice, it significantly reverses the cerebral protective effect of ginsenoside Rb1, indicating that Cav-1 protein mediated the cerebral protective effect of ginsenoside Rb1 on cerebral ischemia reperfusion injury mice.
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Objective: To explore the effect of ginsenoside Rgl on the ubiquitin-modified protein aggregation in the cortex after cerebral ischemia reperfusion (I / R) injury in the rats, and to further clarify the therapeutic mechanism of ginsenoside Rgl in the cerebral I/R injury. Methods: The middle cerebral artery occlusion (MCAO) model was set up with suture method for 1. 5 h of embolization. A total of 72 rats were divided into sham operation group, I/R model group, positive drug control (nimodipine) group, low, middle, and high doses 10, 20, and 40 mg ' k g - 1) of ginsenoside Rgl groups. All 12 rats in each group were given intraperitoneal injection. TTC staining and Longa' s score method were used to detect the infarction areas and the neurological deficit scores of the rats in various groups 24 h after modeling. The death of neurons in the cortex and hippocampus after cerebral ischemia of the rats in various groups were observed with HE staining. Immunohistochemistry and Western blotting method were used to detect the expression of ubiquitin-modified protein aggregation in the cortex of the rats in various groups. Results: Compared with I/R group, the percentages of infarction areas of the rats in nimodipine group and ginsenoside Rgl groups were significantly decreased (P < 0 . 05). and the neurological deficit scores were decreased (P < 0 . 05). The HE staining results showed that compared with sham operation group, the neurons in I/R model group were sparse, showing fragmentation and dissolution; compared with I/R model group, the phenomena of cell nucleus fragmentation, dissolution and powder staining in nimodipine group and different doses of ginsenoside Rgl groups were all improved to different degrees. The immunohistochemical results showed that compared with sham operation group, the positive expression level of ubiquitin-modified protein in I/R model group was increased significantly (P < 0 . 05); compared with I/R model group, the positive expression levels of ubiquitin-modified protein in nimodipine group and different doses of ginsenoside Rgl groups were decreased (P < 0 . 05), especially in high dose of ginsenoside Rgl group (P < 0 . 05). The Western blotting results showed that compared with sham operation group, the level of ubiquitin-modified protein aggregates in I/R model group was significantly increased (P < 0 . 0 5); compared with I/R model group, the levels of ubiquitin-modified protein aggregates in nimodipine group and different doses of ginsenoside Rgl were decreased (P < 0 . 05), especially in high dose of ginsenoside Rgl group. Conclusion: Ginsenoside Rgl can inhibit the formation of ubiquitin-modified protein aggregates induced by I/R injury in the cortex, thereby alleviating the I/R injury in the rats.
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Objective To study the neuroprotective effect of orexin-B on rat model of cerebral ischemia-reperfusion injury and its molecular mechanism. Methods The artery occlusion model of male Wister rats(middle cerebral ar-tery occlusion,MCAO) was established which has been ischemic 2 h and reperfusion 24 h. Rats were randomly di-vided into sham group (control), ischemia-reperfusion group (I/R), ischemia-reperfusion +PBS group (I/R+PBS),and ischemia-reperfusion +orexin-B group (I/R+OXB). The neurological deficit scores were processed to inclusion and exclusion. Infarct size was determined by TTC staining;Using Western blot,the expressions of orexin receptor 2,p-AKT,p-GSK-3β proteins in hippocampus were detected;Jumping test was used to detect learning and memory abilities in rats. Results Orexin-B significantly reduced the volume of cerebral infarction in TTC staining;orexin-B group was significantly increased the expression of orexin receptor 2as well as p-AKT,which decreased p-GSK-3β (P<0.05),compared with the untreated group. Furthmore,the orexin-B treated group can improve the latency period and decline the mistakes in rat Jumping test(P<0.05). Conclusions The neuroprotective effect of orexin-B in cerebral ischemia-reperfusion injury may enhance p-AKT activity and inhibit p-GSK-3β activity,which may increase the proliferation of neurons and improve the cerebral blood glucose concentration.
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The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7–36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7–36) (10, 20, 40 µg/kg i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7–36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7–36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7–36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.
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Animals , Rats , Blood Glucose , Brain , Diet, High-Fat , Hypoglycemic Agents , Infarction , Infarction, Middle Cerebral Artery , Malondialdehyde , Neurons , Neuroprotective Agents , Phosphotransferases , Reperfusion , Reperfusion Injury , Streptozocin , Superoxide DismutaseABSTRACT
Objective To compare the therapeutical effect of puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A on cerebral ischemia reperfusion mice. Methods The mice were randomly assigned for sham group, model group, puerarin group, ligustrazine group, ginsenoside Rb1 group, and Hydroxysafflor yellow A group, 24 mice for each group. All the groups were subjected to middle cerebral artery occlusion (MCAO) by 1 h ischemia and 24 h of reperfusion except the sham group. The puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A were administrated by tail vein injection with 3μmol/kg at the onset of 1 h of ischemia. The neurologic deficit score, infarct area calculated by TTC staining, cerebral cortex blood flow monitored by laser doppler flowmetry, NO content measured by chemical colorimetry and western blot were applied to determine the expression for cleaved-caspase-3 and nuclear transcription factor NF-κB for each group. Results Compared with the model group, the infarct area (15.83%± 1.83%, 22.00%± 2.53%, 22.83%± 1.83%, 17.83%± 1.72%vs. 34.67%± 2.66%) in the puerarin group, ligustrazine group, ginsenoside Rb1 group, Hydroxysafflor yellow A group was significantly decreased (P<0.01 or P<0.05);the cerebral cortex blood flow (598.81 ± 9.90 μl/kg?min-1, 614.78 ± 9.20 μl/kg?min-1, 577.83 ± 5.55 μl/kg?min-1, 583.54 ± 7.98 μl/kg?min-1 vs. 548.43 ± 1.97 μl/kg?min-1) significantly increased (P<0.01 or P<0.05);the NO content (17.09 ± 1.18μmol/L, 18.54 ± 0.54μmol/L, 18.17 ± 0.49μmol/L, 15.10 ± 0.73μmol/L vs. 20.63 ± 0.73μmol/L) ignificantly decreased (P<0.01 or P<0.05);the expression of cleaved-caspase-3 (1.02 ± 0.08, 1.12 ± 0.04, 0.87 ± 0.08, 1.07 ± 0.08 vs. 1.30 ± 0.06) and NF-κB p-p65/NF-κB p65 (1.03 ± 0.19, 1.15 ± 0.05, 1.12 ± 0.08, 0.72 ± 0.08 vs. 1.45 ± 0.08) ignificantly decreased (P<0.01 or P<0.05) Conclusions Four Chinese herbal monomers could improve nerve and cerebral dysfunctions and ameliorate ischemia symptoms with varying degrees. The mechanisms were involved with the enhancement of cerebral cortex blood flow and inhibition of cell apoptosis and the activation of inflammatory signaling pathways.
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Objective To explore the mechanism of high mobility group protein 1 (HMGB1) involved in endoplasmic reticulum stress (ERS) induced by brain ischemia/reperfusion (I/R),based on I/R-HMGB1-ERS as the breakthrough point.Methods The brain of rats birthed 1-3 days was harvested,and the brain cells were cultured in vitro,which were used in the experiment when the cells were in the third passage.The cells were divided into two groups:cells in blank control group were cultured under the normal conditions without any treatment,and the cells in hypoxia/reoxygenation group were cultured with 99.9％ nitrogen for 60 minutes (hypoxia) followed by opening the bottle neck for reoxygenation 120 minutes to simulate I/R model.The HMGB1 gene was silenced by using small interfering RNA (siRNA,siRNA and transfection reagent Lipofectamine 2000 mixture gradient was transfected into the cultured cells) as HMGB1-siRNA transfection group,and blank control (without any treatment) and negative control group (transfected with control siRNA) served as controls.The mRNA and protein expressions of HMGB1 and ERS related molecules were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results ① In cells of hypoxia/reoxygenation group,the mRNA and protein expressions of HMGB1 and ESR related proteins,including glucose regulating protein 78 (GRP78),C/EBP homologous protein (CHOP) and caspase-12,were significantly higher than those of blank control group with statistical difference (the value in blank control group was served as baseline 1,HMGB1 mRNA:3.19±0.48 vs.1,t =2.183,P =0.008;GRP78 mRNA:2.07±0.33 vs.1,t =3.292,P =0.016;CHOP mRNA:1.93±0.28 vs.1,t =2.573,P =0.021;caspase-12 mRNA:2.42±0.42 vs.1,t =2.261,P =0.027:HMGB1 protein:2.28±0.36 vs.1,t =2.042,P =0.009;GRP78 protein:1.33±0.24 vs.1,t =2.781,P =0.016;CHOP protein:1.67±0.34 vs.1,t =2.174,P =0.021;easpase-12 protein:1.36±0.44 vs.1,t =3.192,P =0.008).It was indicated that ERS related molecules involved in cell hypoxia/reoxygenation process.2② After HMGB1 gene was silenced by siRNA,the cells after hypoxia/reoxygenation showed a decrease in the mRNA and protein expressions of HMGB1 and ERS related moleculars as compared with those of blank control group and negative control group (served the value in blank control group as baseline 1,HMGB1 mRNA:0.27±0.12 vs.1,1.02 ± 0.04;GRP78 mRNA:0.16 ± 0.13 vs.1,0.96 ± 0.04;CHOP mRNA:0.47 ± 0.09 vs.1,0.98 ± 0.07;caspase-12 mRNA:0.31 ±0.11 vs.1,1.05±0.02;HMGBI protein:0.23±0.04 vs.1,1.08±0.01;GRP78 protein:0.14±0.09 vs.1,1.35±0.03;CHOP protein:0.32±0.10 vs.1,0.93±0.06;caspase-12 protein:0.27±0.09 vs.1,0.97±0.08;P ＜ 0.05 or P ＜ 0.01).It was indicated that HMGB1 involved in ERS related with GPR7,CHOP,caspase-12.Conclusion Hypoxia/reoxygenation brain intracellular HMGB1 and ERS related molecules expression levels were significantly up-regulated,and silencing HMGB1 gene can significantly inhibit the expression levels of these molecules,and I/R-HMGB 1-ERS pathway may participate in the mechanism of brain I/R injury.
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Objective To compare the strength of oxidative stress from different concentrations of oxygen administered by the accumulation of hydroxyl radicals during early reperfusion after global brain ischemia.Methods Sixteen adult male Mongolian gerbils with microdialysis probes implanted in the hippocampal CA1 were divided randomly (random number)into two groups (n =8 in each).All gerbils of both groups were subjected to 10 min bilateral carotid artery occlusion (BCAO).Then the following intervention:(a) immediate 30% O2 (near normoxia,NO group ) and (b ) immediate 100% O2 (hyperoxia,HO group).The accumulation of hydroxyl radicals (·OH)in hippocampus during reperfusion was estimated by measuring 2,3-dihydroxybenzoic acid (DHBA ) and 2,5-DHBA in microdialysis perfusate.Results Immediately after the onset of reperfusion,two groups showed markedly elevated DHBA,which returned to baseline gradually.Compared with the NO group,the HO group showed significantly higher peak DHBA and slower recovery.Conclusions Hydroxyl radical accumulation was more sensitive to inhalation of high concentration O2 during early reperfusion of global cerebral ischemia.
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Objective To investigate the effects of GM1 and Edaravone on expressions of PDK1,GSK3βprotein in ischemic penumbra after local cerebral ischemia/reperfusion in intraluminal thread occlusion of the middle cerebral artery rats and its related mechanism. Methods The local cerebral ischemia/reperfusion model was established by intraluminal thread occlusion of the middle cerebral artery. The animals were randomly divided into pseudo surgery group,model group,GM1 group, Edaravone group and GM1 and Edaravone group. Using the techniques of immu-no-histochemical sraining,the expressions of PDK1,GSK3β protein were observed at 3,7 and 14 days in ischemic penumbra. Results In ischemic penumbra,3,7,14 days each time point,a value and positive unit of the PDK1 protein expression in GM1 and Edaravone groups were higher than those in GM1 or Edaravone groups(P<0. 05), model groups(P<0. 01);a value and positive unit of the GSK3βprotein expression in GM1 and Edaravone groups were lower than those in GM1 or Edaravone groups(P<0. 01),model groups (P<0. 01). Conclusion GM1 and Edaravone resist neural cell apoptosis,regulate PI3K /Akt signal transduction pathway by enhancing PDK1 protein and restraining GSK3β expression after local cerebral ischemia /reperfusion in artery rats.
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Objective: To study the protection and mechanisms of effective fraction from Buyang Huanwu Decoction (EFBHD) on rat brain after cerebral ischemia-reperfusion injury. Methods: Rat model of cerebral ischemia-reperfusion injury was created by the middle cerebral artery occlusion (MCAO) by modified suture method. Healthy male SD rats were randomly divided into six groups: Sham-operated group, model group, high-, middle-, and low-dose (200, 100, and 50 mg/kg) of EFBHD groups, and positive control group (treated with EGB 100 mg/kg). The neurological deficit symptom scores were observed and the infarct volume was measured by triphenyltetrazolium chloride (TTC) staining in 24 h after the cerebral ischemia. The contents of TNF-α, IL-1β, and IL-6 in serum were measured by enzyme-linked immunosorbent assay (ELISA) methods. In addition, the activity of LDH and MDA content in serum were determined by abdominal arterial blood and centrifuged. Results: Compared with the model group, EFBHD could significantly improve the neruological dysfuction, decrease the cerebral infarct volume, and inhibit the activity of LDH, and reduce the contents of MDA, TNF-α, IL-1β, and IL-6 in serum (P<0.01, 0.05). Conclusion: EFBHD has significant protection on cerebral ischemia-reperfusion injury in rats, which may be related to the inhibition of inflammatory cytokine secretion and expression and inducing the inflammation in brain tissue.
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To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-1beta, IL-6, and TNF-alpha) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-1beta, IL-6, and TNF-alpha levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model.
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Animals , Rats , Brain , Brain Injuries , Colostrum , Cytokines , Eating , Interleukin-6 , Milk , Neuroprotective Agents , Rats, Sprague-Dawley , Reperfusion , Salicylamides , Tumor Necrosis Factor-alphaABSTRACT
Aim To investigate the effect of fenofibrate on focal cerebral ischemia injury in rats and its mechanism.Methods The rat model of global cerebral ischemia/reperfusion injury was established by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension.Fenofibrate (33, 100, 300 mg·kg~(-1)) was intragastriclly administered 30 min before the operation, MK886 (6 mg·kg~(-1)) was given intraperitoneally 30 min before administration of fenofibrate (300 mg·kg~(-1)).Morris water maze was used to evaluate the ability of spatial learning and memory function.HE staining was used to observe pathological morphological changes of hippocampal neurons. NF-κBp65 expression was detected by immunohistochemistry, SOD activities and MDA contents were analyzed by biochemistry, and IL-1β, IL-6, IL-10, TNF-α levels were detected by ELISA.Results Fenofibrate remarkably improved the spatial learning and memory function, obviously prevented the hippocampal neurons from karyopycnosis and losing induced by I/R. Fenofibrate significantly blunted the increase of MDA, NF-κBp65, TNF-α, IL-1β, IL-6, and the decrease of IL-10 and SOD activities of I/R rats.Conclusions Fenofibrate has an obviously neuroprotective effect on global cerebral ischemia/reperfusion damage by activating PPARα.The anti-inflammation and antioxidative stress of fenofibrate may be involved in the protective mechanism.
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AIM: To observe the neuroprotective effect of combined treatment with taurine and diazepam against focal cerebral ischemia-reperfusion in rats. METHODS: Sixty male Sprague-Dawley rats were randomly divided into five groups: sham-operation group, vehicle group, taurine group (200 mg/kg, ip), diazepam group (10 mg/kg, ip) and combined treatment group (taurine 100 mg/kg+diazepam 5 mg/kg). Focal cerebral ischemia was induced by the method of middle cerebral artery occlusion (MCAO) in rats, and reperfusion was emerged by removing the thread 2 h later. The drugs were administered respectively at the time of reperfusion, and subsequently repeated once 12 h later. The animals in vehicle group were intraperitoneally injected with isodose normal saline. The neurological deficit score, the brain water content and cerebral infarction were measured 48 h after MCAO. Other 5 group animals of focal cerebral ischemia-reperfusion (n=16 in each group) were set up as mentioned above and accepted treatments 10 h after reperfusion, likewise repeated once 12 h later. Twelve animals in each group were adopted the same management as the previous 5 groups at 48 h after MCAO. The remained 4 animals in each group were sacrificed until two weeks after MCAO to observe the histopathological changes by nissl staining. RESULTS: Compared to vehicle group, the animals in combined treatment group at 2 h or 12 h after MCAO both decreased the neurological deficit score, reduced the brain water content and infarct volume (P<0.01 or P<0.05). The combined treatment significantly alleviated the neurological necrosis as well. The neuroprotective effect of the combined treatment was superior to that of using taurine or diazepam alone. CONCLUSION: These results suggest that combination of taurine and diazepam treatment has a coordinate neuroprotective effect on both the acute and chronic brain damage of focal cerebral ischemia-reperfusion.
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@#The cerebral ischemia reperfusion injury is one of factors in aggravating brain injury, and the inflammatory response is one of the main reasons in the reperfusion injury after acute cerebral ischemia. Inflammation is modulated by many factors such as inflammatory mediators and inflammatory cells that promote brain damage from ischemia injury to reperfusion injury. This paper would review the role of inflammatory cells and mediators such as cytokines, chemotactic factors, adhesion molecules on cerebral tissue injury.
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@#ObjectiveTo investigate the effects of Angelica sinensis on the expression of vascular endothelial growth factor (VEGF) Flt-1, Flk-1 mRNA after the brain ischemia-reperfusion injury in rats.MethodsWistar rats were randomly divided into the group A, group B and normal control group. The group A underwent middle cerebral artery occlusion (MCAO) for 2h by suture, group B underwent MCAO for 2h meanwhile received treatment with Angelica sinensis (5 g/kg). Immunohistochemistry and quantitative reverse transcription and polymerase chain reaction (RT-PCR) technique were used to examine the gene expression of VEGF.ResultsThe result of immunohistry revealed that VEGF in the group A and group B reached its peak at 24 h after reperfusion then declined gradually. The result of RT-PCR manifested that the gene expression of VEGF in the group A increased from 3 h after reperfusion and reached its peak at 6 h; in the group B reached its peak on the 3rd day. The expression of VEGF in the group B was significantly increased than group A at the same time point.ConclusionAngelica sinensis can enhance the expression of Flt-1, Flk-1 after transient interruption of cerebral blood flow in rats.
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Aim To study the effects of amitriptyline(Ami)on focal cerebral ischemia-reperfusion injury in rats.Methods An animal model of focal cerebral ischemia-reperfusion injury was induced by the middle cerebral artery occlusion(MCAO) by reversibly inserting a nylon thread method.The rats were decapitated after ischemia for 1 hour and reperfusion for 2 hours.The infarct volumes were determined using a 2,3,5-tri-phenyl tetrazolium chloride(TTC) staining and assessed by image analysis system.The neurologic deficit status were evaluated on 0~5 grade scale.The levels of dopamine(DA),norepinephrine(NE),serotonin(5-HT) and its metabolic product~hydroxyindole acetic acid(5-HIAA) in cortex and striatum were measured by fluoro-spectrophotometry.Results Ami treatment exhibited a remarkable reduction in infarct volume and neurologic deficit scores.The monoamines content of cortex and striatum had a significant increase compared with ischemia-reperfusion group.Conclusion Amitriptyline has protective effect on cerebral ischemia-reperfusion injury in rats.The mechanism might be related to reducing the release of NE,DA and 5-HT during cerebral ischemia-reperfusion,attenuating or inhibiting of the neurotoxic effects of monoamine neurotransmitters.
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Objective To explore the expression of syndecan-1 in different intervals following focal cerebral ischemia/reperfusion in rat and the relationship between syndecan-1 and inflammatory cells in the rat brain.Methods The rat model of middle cerebral artery occlusion(MACO) was performed by using the intraluminal filament occlusion for 2 h,then released.The rat brain were cut in the coronal planes at the levels of the hippocampus as the templates.The immunohistochemical staining and HE staining were used to observe the distribution and the quantity of syndecan-1 and inflammatory cell expression in the normal control group,sham operation group and the MCAO groups at 4,24,72 h and 7 d after reperfusion.Results The expression of syndecan-1 was mainly in the cortex and the subcortex in the rats of normal control group and sham operation group.The immunoreactivity of syndecan-1 in the infarcted core and perilesional infarcted zone started decreasing at 4 h after ischemia/reperfusion,reached the lowest at 24 h.The expression of syndecan-1 in the perilesional infarcted zone was up-regulated at 72 h and recovered at 7 d.The relationship between syndecan-1 and inflammatory cells was of negative correlation.Conclusion The decreasing of syndecan-1 may contribute to inflammatory response in the cerebral infarction region after focal cerebral ischemia/reperfusion.
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Objectives: To study the protective effects of Nao Mai Tong(NMT) on middle cerebral artery occlusion(MCAO) induced focal brain ischemia reperfusion injury in rats. Methods: After rats were respectively given NMT 1 g/kg, 3 g/kg, 9 g/kg ig everyday for 1 week, the effects of NMT on the histological changes and behavior disorder caused by focal brain ischemia reperfusion which was made by occlusion of middle cerebral artery were investigated. The gasping time after the cutting of the head in ischemia reperfusion rat was recorded. The contents of ATP and LA were determined by radioimmunoassay. Results: NMT significantly reduced the extent of behavior disorder, descended the rate of cerebral infarction area, and improved histological injury of brain tissues. The grasping time after head cutting was prolonged. It was found that the level of ATP was increased and LA was decreased markedly. Conclusions: NMT shows a significant protective effect on histological, behavior and energy metabolic consequences of MCAO induced focal brain ischemia reperfusion injury.
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Objective To investigate the dynamic changes of ATP content in rat cerebral cortex after transient ischemia followed by reperfusion and the relationship between the change of energy and the recovery of neural function.Methods The rats were subjected to 10 min of middle cerebral artery occlusion (MCAO). At the time point of 0 h, 1 h, 3 h, 6 h, 12 h, 24 h and 72 h after reperfusion, ATP contents of frontal and parietal cortex were measured by capillary zone electrophoresis.Results At the end of 10 min ischemia, ATP content fell dramatically to less than 20% of the control level. After reperfusion, ATP content recovered gradually. After 1 h, 3 h, 6 h and 12 h of reperfusion, ATP content returned to 70.5%, 65.7%, 84.8% and 86.9% of the control level ( P=0.052, 0.030, 0.332 and 0.491). From 24 h on until 72 h after reperfusion, ATP content decreased again, reaching half of the control level ( P=0.003 and P=0.023). After 10 min ischemia, limb function recovered gradually and completely at last. From 24 h on until 72 h after reperfusion, unwillingness of action and eating was found.Conclusions The recovery of cellular energy system function is delayed even though the reperfusion is in time after transient cerebral ischemia. Furthermore, secondary failure of cellular energy system function occurrs with the reperfusion proceeding. These phenomena are probably responsible for the delayed recovery of neural function after cerebral ischemia in spite of reperfusion.