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OBJECTIVE：To study the improvement effects of icariside Ⅱ（ICS Ⅱ）on neurological function of focal cerebral ischemia model rats by regulating miR- 141-3p/Notch/nuclear factor erythroid- 2-related factor 2（Nrf2）axis（miR-141-3p/Notch/ Nrf2）. METHODS ：The rats were divided into sham operation group ，model group ，nimodipine group （20 mg/kg）and ICS Ⅱ low-dose，medium-dose and high-dose groups （4，8，16 mg/kg），with 20 rats in each group. Twenty-four hours after establishing focal cerebral ischemia model ，model rats were given re levant medicine or normal saline intragastrically ，twice a day ，for consecutive 3 d. The neurological deficit of rats in each group was scored ；the volume of cerebral infarction was measured by 2，3， 5-triphenyltetrazolium chloride （TTC）staining；water content of cerebral tissue and the permeability of blood-brain barrier were measured；HE staining was performed to observe the pathological change of cerebral tissue of rats ；the expression of miR- 141-3p in cerebral tissue of rats was measured by qRT-PCR ；the protein expression of Notch and Nrf 2 in cerebral tissue of rats were measured by Western blotting assay. RESULTS ：Compared with sham operation group ，the neurological deficit score ，expression of Notch-1 and Nrf 2 in model group were significantly lowered （P＜0.05）；infarction volume ，brain water content ，the permeability of blood-brain barrier and the expression of miR- 141-3p in cerebral tissue were increased significantly （P＜0.05）；the distribution of cortical cells was disordered ，and inflammatory infiltration and necrosis were observed in a large number of nerve cells. Compared with model group ，the neurological deficit score ，the protein expression of Notch- 1 and Nrf 2 in cerebral tissue were significantly increased in ICS Ⅱgroups（P＜0.05）；infarction volume ，brain water content ，the permeability of blood-brain barrier and the expression of miR- 141-3p in cerebral tissue were decreased significantly （P＜0.05）；the arrangement of cortical cells was regular，and the inflammatory infiltration and necrosis of nerve cells were decreased significantly. CONCLUSIONS ：ICS Ⅱ can promote the recovery of neurological function in focal cerebral ischemic model rats ，which may be related to down-regulation of miR-141-3p and activation of Notch/Nrf 2 axis.
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Objective To study the regulating effect of freeze-dried substances of Salvia miltiorrhiza and Ligusticum chuanxiong Decoction on lipid metabolism abnormality in focal cerebral ischemia rats. Methods The focal cerebral ischemia rat model was established by monofilament method. The rats were randomly divided into normal group, sham operation group, model group, and drug treatment group. Plasma was collected after the last dosage and UPLC-Q/TOF-MS was used to study the plasma lipidomics. The lipidomics data were analyzed by orthogonal partial least square discriminant analysis (OPLS-DA), and the lipid metabolites changes were examined before and after the intervention of S. miltiorrhiza and L. chuanxiong. Results The focal cerebral ischemia rat model was successfully repeated. The S. miltiorrhiza and L. chuanxiong Decoction freeze-dried substances obviously reversed the abnormal lipid metabolism profile in the focal cerebral ischemia rat model. The plasma lipid biomarkers of ischemia injury rat were PS (21:0/0:0), PG (12:0/17:0), C16 sphinganine, phytosphingosine, PE [18:1 (9Z)/0:0], PC (16:1/2:0), PC (0:0/18:0), PC (16:1/0:0), PC (16:0/0:0), PC (18:2/0:0), PC (18:1/0:0), PC (18:0/0:0), and PC (20:5/0:0), respectively. Conclusion S. miltiorrhiza and L. chuanxiong Decoction freeze-dried substances have protective effects on cerebral ischemia injury, which may be related to the regulation of abnormal lipid metabolism, especially for phosphatidylcholines (PCs).
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OBJECTIVE: To observe the effect of manual acupuncture (MA)＋ electroacupuncture (EA) on changes of neurological function and expression of monocarboxylate transporter 2(MCT2)in cerebral ischemia (CI) rats, so as to explore its mechanism underlying improvement of ischemic cerebrovascular disease. METHODS: Eighty male Wistar rats were equally randomized into four groups: normal control (normal), sham operation (sham), model and acupuncture. The CI model was induced by middle cerebral artery occlusion (MCAO) with a thread embolus. Manual acupuncture stimulation (mild twisting reinforcing-reducing method) was applied to "Baihui"(GV20)and "Fengfu"(GV16) for 10 min. EA (1 mA, 2 Hz /15 Hz) was respectively applied to bilateral "Quchi" (LI11) and "Zusanli"(ST36) for 20 min, once per day for 7 days. The neurological deficit severity was evaluated according to Zea Longa's methods. The activity of lactate dehydrogenase (LDH), fructose-6-phosphate kinase (PFK) and pyruvate kinase (PK) in the peri-ischemic cortex tissue was detected by enzymatic chemistry, and the expression of MCT2 detected by immunofluorescence histochemistry, Western blot and quantitative real-time PCR, separately. RESULTS: After CI and in comparison with the normal and sham groups, the Zea Longa's score, the fluorescence intensity and the expression level of MCT2 protein were significantly increased (P0.05). Following the intervention and in comparison with the model group, the Zea Longa's score was considerably decreased in the acupuncture group (P<0.01), the activity of LDH, PFK and PK，and the expression levels of MCT2 protein and mRNA were considerably or further up-regulated in the acupuncture group (P<0.01, P<0.05). CONCLUSION: Acupuncture intervention can improve neurological function in CI rats, which is possibly related with its effects in up-regulating the expression of MCT2 and promoting the utilization of lactate in peri-ischemic cortex.
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Objective To explore the effect of sufentanil postconditioning on the focal cerebral is-chemia reperfusion injury in diabetic rats. Methods An intraperitoneal injection of 50 mg/kg streptozotocin was used to induce diabetes in rats. Meanwhile,the diabetes mellitus model was confirmed by the blood glu-cose level over 16. 7 mmol/L. The diabetes mellitus male SD rats,weighting 250-300 g,were randomly divid-ed into 3 groups:sufentanil postconditioning diabetic group (SP-DM),ischemia reperfusion diabetic group (IR-DM),sham operation diabetic group(sham-DM),with 12 in each group. The non-diabetic rats were randomly divided into 3 groups:sufentanil postconditioning non-diabetic group(SP-NDM), ischemia reperfu-sion non-diabetic group(IR-NDM),sham operation non-diabetic group(sham-NDM),with 12 in each group. All rats in the IR-NDM/DM group and SP-NDM/DM group were exposed to the right middle cerebral artery occlusion for 90 minutes followed by 24 hours reperfusion. The sufentanil 1 μg/kg were injected into the rats in SP-NDM/DM group via tail vein at 5 minutes before reperfusion. Normal saline was injected into the rats in sham-NDM/DM group and IR-NDM/DM group at 5 minutes before reperfusion. At 24 hours after reperfu- sion,the neurological deficit scores( NDS) were assessed,then all the rats were sacrificed. Infarct volume, which was determined by 2,3,5-triph-enyltetrazolium ( TTC) staining,and water content of right hemisphere for brain edema were also measured. Results All rats showed neurological deficit,brain infarction and brain edema after focal cerebral ischemia reperfusion. (1) At 24 hours after reperfusion,the neurological deficit score in IR-DM group(3. 4±0. 4) was significantly higher than that in the IR-NDM group(2. 8± 0. 5) ( t=2. 313,P<0. 05),there was no significant difference in neurological deficit score between the SP-DM group (3. 3±0. 4) and the IR-DM group(t=1. 546,P>0. 05). (2) At 24 hours after reperfusion,the infarct volume in IR-DM group((58. 3±2. 1)%) was significantly higher than that in the IR-NDM group((32. 1±2. 6)%) (t=2. 912, P<0. 05), there was no significant difference in infarct volume between the SP-DM group ((56. 9±2. 1)%) and the IR-DM group(( 58. 3 ± 2. 1)%) ( t=1. 633,P>0. 05). ( 3) At 24 hours after reperfusion,the water content of the right hemisphere in IR-DM group(( 89. 3± 3. 5)%) was significantly higher than that in the IR-NDM group((82. 6±3. 9)%)(t=2. 218,P<0. 05),there was no significant differ-ence in water content of the right hemisphere between the SP-DM group(( 87. 5±3. 4)%) and the IR-DM group(t=1. 730,P>0. 05). Conclusion Sufentanil postconditioning loses neuroprotection against focal cer-ebral ischemia reperfusion injury in diabetic rats.
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Animals , Mice , Apoptosis , Blotting, Western , Brain Ischemia , Brain , Caspase 3 , DNA Nucleotidylexotransferase , Heme Oxygenase-1 , Infarction, Middle Cerebral Artery , Reactive Oxygen Species , Reperfusion , Stroke , Up-Regulation , WaterABSTRACT
OBJECTIVE@#To observe the effect of electroacupuncture (EA) on the expressions of growth arrest-specific protein 7 (Gas7) and nerve growth factor (NGF) in arcuate nucleus (ARC) of rats with focal cerebral ischemia and explore the potential action mechanism of EA in treatment of focal cerebral ischemia.@*METHODS@#A total of 50 SD rats were randomized into 4 groups, named a normal group ( =12), a sham-operation group ( =12), a model group ( =14) and an EA group ( =12). In the model group and the EA group, the thread embolization method was adopted to duplicate the model of the right middle cerebral arterial embolism. In the sham-operation group, the skin of the neck was opened and sutured without any other intervention. In the EA group, EA was applied to "Baihui" (CV 20) and "Zusanli" (ST 36) on the left side, once a day, 30 min each time, consecutively for 21 days, while there was no any intervention in the normal group, the sham-operation group and the model group. Using the immunohistochemistry (IHC) method and Western blot method, the expressions of Gas7 and NFG of ARC on the ischemic side were determined. Using Nissle staining, the morphological changes in ARC neurons were observed.@*RESULTS@#The results of Nissle staining showed that there was no significant change in the morphology of ARC neurons in the normal group and the sham-operation group. In the model group, the volume of neuron cells was atrophied obviously and the cells were arranged irregularly. In the EA group, the morphology of ARC neuron was similar to the normal group. The results of IHC and Western blot indicated that the expressions of immunoreactive neurons and protein of Gas7 and NGF in ARC of the rats in the model group were increased obviously as compared with the normal group and the sham-operation group and the expressions in the EA group were further enhanced as compared with the model group (all <0.05).@*CONCLUSION@#Gas7 and NGF may be participated in the compensatory process of partial protection of the body in the patients with focal cerebral ischemia. EA up-regulates the expressions of Gas7 and NGF in ARC, which may be one of the neuroprotective mechanisms of EA in treatment of cerebral ischemia.
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Animals , Humans , Rats , Brain Ischemia , Metabolism , Therapeutics , Cerebral Infarction , Metabolism , Therapeutics , Electroacupuncture , Nerve Growth Factor , Metabolism , Nerve Tissue Proteins , Metabolism , Rats, Sprague-DawleyABSTRACT
Objective:To observe the changes of inflammatory damage in the brain of rats after focal cerebral ischemia-reperfusion, and explore the effect of the initiation of IκB kinases β (IKKβ), which is the key protein of activating nuclear factor (NF)-kappa B signaling pathway in inflammatory response, and the mechanism of electroacupuncture inhibiting inflammatory damage. Methods:A total of 240 male Sprague-Dawley rats were randomly divided into sham group, ischemia-reperfusion group, electroacupuncture group, IKKβ silencing group, IKKβ overexpression group and IKKβ overexpression + electroacupuncture group, each group was further divided into six hours, twelve hours, 24 hours, 48 hours and 72 hours subgroups. The right middle cerebral artery occlusion reperfusion model was established by modified thread embolization. The IKKβ gene was intervened by gene silencing and gene overexpression technology. Results:Compared with the model group, the neurological function score increased (P < 0.05), the cerebral infarction volume decreased (P < 0.05), the activation of NF-κB p65 was inhibited, and the content of proinflammatory factors decreased (P < 0.05) in IKKβ silencing group. Compared with IKKβ silencing group, the above results were significantly worse in IKKβ overexpression group (P < 0.05), and microglia in cerebral ischemic cortex were significantly activated. The activation of microglia and activation of IKKβ were significantly inhibited in IKKβ overexpression + electroacupuncture group. Conclusion:IKKβ gene silencing could inhibit the inflammatory response of cerebral ischemic cortex mediated by NF-κB signaling pathway, and over-expression of IKKβ could lead to severe inflammatory damage in ischemic cortex. Electroacupuncture could inhibit the inflammatory damage after focal cerebral ischemia-reperfusion by regulating the activity of IKKβ.
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Aim To investigate the effects of isoflu-rane on angiogenesis in rats with cerebral ischemia/reperfusion and the possible mechanism. Methods Forty healthy adult male Sprague-Dawley rats were randomly divided into sham operation group (Sham group) , ischemia-reperfusion group (I/R group) , isoflurane post-treatment group (ISO group) and isoflurane post-treatment + Smad3 specific inhibitor SIS3 HC1 group (ISO + SIS3 group). Rat middle cerebral artery occlusion model (MCAO) was established by suture method. After 24 h, Zea-Longa method was used to evaluate the neurological deficit of rats. HE staining was used to evaluate the pathological damage of brain tissues. Nissl staining was used to evaluate the surviving neurons in ischemic brain tissues. TUNEL staining was employed to assess the apoptosis of brain tissues. Immunofluorescence was applied to evaluate the expression levels of VEGF and CD34. Western blot analysis was used to detect the expression levels of p-Smad3, Smad3 , VEGF and CD34. Results Isoflurane significantly reduced the neurobehavioral score of rats, reduced the pathological damage of brain tissues, increased the number of normal neurons in the ischemic brain tissues, reduced the apoptotic cells in injured brain tissues, and enhanced the expression levels of p-Smad3, VEGF and CD34. Smad3 inhibitor re-versed the brain protective effect of isoflurane, aggravated cerebral ischemia-reperfusion injury, and inhibited the protein expression levels of p-Smd3 , VEGF and CD34. Conclusions Isoflurane can improve cerebral ischemia/reperfusion injury in rats, and its protective mechanism is related to activation of Smad signaling pathway, promotion of VEGF and CD34 protein expression , and promotion of angiogenesis.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) and EA combined with intracerebral injection of vascular endothelial growth factor (VEGF) on endoplasmic reticulum stress (ERS) related proteins and genes as activating transcription factor (ATF 6), inositol requiring enzyme-1 (IRE 1), CCAAT/enhancer binding protein homologous protein (CHOP), X box-binding protein-1 (XBP 1) of cerebral ischemia reperfusion injury (CIRI) rats, so as to study its repair effect for CIRI. METHODS: Forty male SD rats were equally and randomly divided into 5 groups: sham operation, model, EA, VEGF and EA+VEGF groups (n=8). The CIRI model was established by occlusion of the middle cerebral artery (MCAO) with thread embolism method. For rats of the sham operation group, the right common carotid artery was isolated without MCAO. EA (2 Hz/100 Hz, 1-3 mA) was applied to "Baihui" (GV 20), left "Quchi" (LI 11) and left "Zusanli" (ST 36) for 30 min, once a day for 14 days. For rats of the VEGF and EA+VEGF groups, 10 µL VEGF (0.025 µg/µL) was injected into the lateral ventricle 24 h after successful modeling. The rats' neurological function was assessed by using the modified neurological severity score (mNSS), and the histopathological changes of cerebral tissue were observed by Nissl staining method. The expression levels of ERS related proteins and genes ATF 6, IRE 1, XBP 1 and CHOP were determined by western blot (WB) and fluorescent quantitative PCR, separately. RESULTS: After modeling, the level of mNSS was significantly higher in the model group than in the sham operation group (P<0.05), and the number of Nissl bodies was markedly lower in the model group than in the sham operation group (P<0.05). Following the treatment, the mNSS was significantly lower in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05), and the numbers of Nissl bodies were obviously higher in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05), suggesting an improvement of neurological dysfunction and a repair of the injured cerebral tissue after the treatment. The levels of CIRI-induced increase of mNSS and CIRI-induced decrease of the number of Nissl bodies in the EA+VEGF group were respectively remarkably lower or higher than those of the simple EA and simple VEGF groups (P<0.05). WB and PCR showed that the expression levels of ATF 6, IRE 1, XBP1 and CHOP proteins and genes were notably higher in the model group than in the sham operation group (P<0.05), and considerably lower in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05). Comparison among the three treatment groups showed that after the treatment, the expression levels of ATF 6, IRE 1, XBP1 and CHOP proteins and genes were obviously lower in the EA+VEGF group than in the EA and VEGF groups (P<0.05). CONCLUSION: EA and EA plus intracerebral microinjection of VEGF can improve neurological function and promote cerebral tissue repair in CIRI rats, which is associated with their effects in down-regulating the expression of ERS related proteins ATF 6, IRE 1, XBP1 and CHOP. The effect of EA+VEGF is superior to that of simple EA and simple VEGF.
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<p><b>OBJECTIVE</b>To investigate the effects of the flower buds extract of Tussilago farfara Linné (Farfarae Flos; FF) on focal cerebral ischemia through regulation of inflammatory responses in activated microglia.</p><p><b>METHODS</b>Brain ischemia was induced in Sprague-Dawley rats by a transient middle cerebral artery occlusion (tMCAO) for 90 min and reperfusion for 24 h. Twenty rats were randomly divided into 4 groups (n=5 per group): normal, tMCAO-induced ischemic control, tMCAO plus FF extract 300 mg/kg-treated, and tMCAO plus MK-801 1 mg/kg-treated as reference drug. FF extract (300 mg/kg, p.o.) or MK-801 (1 mg/kg, i.p.) was administered after reperfusion. Brain infarction was measured by 2,3,5,-triphenyltetrazolium chloride staining. Neuronal damage was observed by haematoxylin eosin, Nissl staining and immunohistochemistry using anti-neuronal nuclei (NeuN), anti-glial fibrillary acidic protein (GFAP), and anti-CD11b/c (OX42) antibodies in ischemic brain. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), and hypoxia-inducible factor-1a (HIF-1α) were determined by Western blot. BV2 microglial cells were treated with FF extract or its main bioactive compound, tussilagone with or without lipopolysaccharide (LPS). Nitric oxide (NO) production was measured in culture medium by Griess assay. The expressions of iNOS, COX-2 and pro-inflammatory cytokines mRNA were analyzed by reverse transcription-polymerase chain reaction. The expression of iNOS, and COX-2 proteins, the phosphorylation of ERK1/2, JNK, and p38 MAPK and the nuclear expression of NF-κB p65 in BV2 cells were determined by Western blot.</p><p><b>RESULTS</b>FF extract significantly decreased brain infarctions in ischemic rats (P<0.01). The neuronal death and the microglia/astrocytes activation in ischemic brains were inhibited by FF extract. FF extract also suppressed iNOS, TNF-α, and HIF-1α expression in ischemic brains. FF extract (0.2 and 0.5 mg/mL, P<0.01) and tussilagone 20 and 50 μmol/L, P<0.01) significantly decreased LPS-induced NO production in BV2 microglia through downregulation of iNOS mRNA and protein expression. FF extract and tussilagone significantly inhibited LPS-induced expression of TNF-α, IL-1β, and IL-6 mRNA, and also suppressed the phosphorylation of ERK1/2, JNK and p38 MAPK and the nuclear expression of NF-κB in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>FF extract has a neuroprotective effect in ischemic stroke by the decrease of brain infarction, and the inhibition of neuronal death and microglial activation-mediated inflammatory responses.</p>
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Objective Apoptosis was induced by oxidative stress in nerve cells after cerebral ischemia. It further breaks the dy-namic balance of mitochondrial division of fusion. This study aimed to investigate the effect of butylphthalide combined with edaravone treat-ment on the dynamic change of Drp1 and Mfn2 in rats with focal cere-bral ischemia cells and its protection mechanism. Methods 96 rats were divided into 4 groups according to random number table. The 4 groups were ischemia group,butylphthalide group,edaravone group and butylphthalide combined with edaravone groups(combine group),each group divided into three subgroups(3 d,7 d,14 d). Longa-Zea suppository method is adopted to establish the middle cerebral artery occlusion(MCAO)model.Butylphthalide group,edar-avone group and combine group were injected butylphthalide(0.4 g/kg)and/or edaravone(10 mL/kg)peritoneally 2 hours before surgery and 1 day after surgery. The same volume of isotonic saline was given at the same time of the other 3 groups in ischemia group. The cerebral cortex of the left ischemic region was obtained at the day 3,7,14. The evaluation of the curative effect was evaluated with neurological function score.HE staining was used to observe the cerebral cortex neuron morphological structure,protein and mRNA lev-el of Drp1 and Mfn2 was measured by western blot and RT-PCR. Results At the day 3,7,and 14,the neurological function score was higher in ischemia group than the other 3 groups(P<0.05). Compared with the combine group at day 3,7,and 14[(1.06± 0.18),(0.82±0.13),(0.57±0.10)],the neurological function score was elevated in butylphthalide group[(2.02±0.18),(1.23± 0.13),(0.86±0.10)]and edaravone group[(2.08±0.17),(1.23±0.13),(0.85±0.12)](P<0.05). At the same time point,com-pared with the ischemia group,Drp1 protein and mRNA levels were lower in the other 3 groups(P < 0.05)while Mfn2 protein and mRNA levels were elevated(P<0.05). Compared with the butylphthalide group and edaravone group,Drp1 protein and mRNA levels were lower in combine group(P<0.05)while Mfn2 protein and mRNA levels were elevated(P<0.05). Conclusion The protective effect of edaravone combined with butylphthalide is better than single use. Its mechanism may be related to the removing of oxygen free radicals and reducing oxidative stress by edaravone,and the protection of the mitochondria by butylphthalide.
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Objective To investigate the establishment of focal cerebral ischemia model in rabbits with the improved suture method.Methods A total of 45 healthy and clean adult New Zealand rabbits were divided into either a sham operation group (n =5) or a model group (n =40) using random number table method before modeling,and the sex was not limited.The self-made head ends of 2-0 fishing lines dipped in paraffin were used as the sutures.The external carotid artery was cut and inserted into a intracranial artery through the internal carotid artery and blocked the origin of middle cerebral artery.The neurological function score was performed after 6 h.The neurological deficit scores ≥2 was successful modeling.The rabbits were killed by anesthesia.The brain slices were stained with 2％ 2,3,5-triphenyl tetrazolium chloride solution.The infarct foci were observed.The diameters of suture head and the depth of suture insertion were compared in the model rabbits with successful modeling,failure,and death in the model group.Results There were 40 rabbits in the model group,six of them died,including 4 died of subarachnoid hemorrhage within 4 h after operation,and 2 died from anesthetic accident.The mortality rate was 15.0％.Seven rabbits failed,mainly because of cerebral vasospasm and the insertion depth of suture was insufficient.Twenty-seven had successful modeling,and the success rate was 67.5％.All the rabbits in the sham operation group survived.The diameter of the suture head and insertion depth in the successful modeling rabbits were compared with the death and failure outcome in rabbits.The difference was statistically significant (diameter:0.52 ± 0.14 mm vs.0.45 ±0.40 mm and 0.58 ±0.17 mm;depth:5.49 ±0.17 cm vs.6.04 ± 0.11 cm and 4.26 ±0.30 cm;all P ＜ 0.05).Conclusions The improved suture method can successfully prepare the focal cerebral ischemia model of middle cerebral artery in rabbits.The method is simple.Its repeatability and practicability are better.
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Objective To evaluate the effects of Xifeng Dingxuan granules on behavioral changes and brain energy metabo?lism on focal incomplete cerebral ischemia vertigo model rat. Methods Experimental rats were divided into normal control group, sham operation group,model group,flunarizine hydrochloride group(0.5 mg/kg),ginkgo leaf group(8 mg/kg)and Xifeng Dingxuan granule groups(0.27,0.54 and 1.08 g/kg). The drugs were all administered intragastrically. During the experimental period,step-down test was conducted to monitor the escape latency of rats from electrical stimulation,and the blood flows in right brain vestibular nucleus were measured. At the end of the experiment,the levels of the lactate(LAC),lactic acid dehydrogenase(LDH),superoxide dismutase(SOD)and malondialdehyde(MDA)in brain tissue were determined by colorimetry. Results 1. Compared with the normal control group,the escape latency of rats from electrical stimulation in model group was significantly prolonged(P<0.01). The escape latency was significantly reduced by the treatment of Xifeng Dingxuan granules(P<0.01),and the dosage of 0.54 g/kg was most effec?tive. 2. Compared with the sham operation group,the blood flow of right brain vestibular nucleus in the model group was decreased (P<0.01). The decreased blood flow could be alleviated by the treatment of Xifeng Dingxuan granules and the dosage of 0.27 g/kg was most effective(P<0.01). 3. Compared with sham operation group,the contents of LAC and LDH in the right brain tissue were signifi?cantly increased in the model group(P<0.01). Compared with the model group,the contents of LAC and LDH were decreased signifi?cantly by the treatment of Xifeng Dingxuan granules with the dosage of 0.27 g/kg and 0.54 g/kg(P<0.01). 4. Compared with the sham operation group,the content of MDA and the activity of SOD in the right brain tissue were significantly increased in the model group (P<0.01)and could be alleviated by the treatment with Xifeng Dingxuan granules at each dose(P<0.01). Conclusion The results indicated that Xifeng Dingxuan granules could suppress the decrease of blood flow in vestibular nucleus,improve the brain energy me?tabolism and reduce the oxidative stress response in focal incomplete cerebral ischemia vertigo rat model ,which implicated the possi?ble therapeutic effect of Xifeng Dingxuan granules on the vertigo.
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Objective To investigate the effect of leptin on endoplasmic reticulum stress related protein after focal cerebral ischemia in rats. Methods Ischemia was induced by occluding the middle cerebral artery in rats brain using the filament occlusion method. Forty SD rats were randomly divided into sham operation group, cerebral is-chemia group and leptin-preconditioning group. Leptin was injected subcutaneously before occlusion of blood vessel. Longa 5 score neurological function scale, body weight and brain edema changes were measured 6 hours after MCAO, and the brain was removed to detect the endoplasmic reticulum marker protein: glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) by immunohistochemical method. Results There was no difference in the body weight changes between leptin-preconditioning group and ischemic group. In the leptin-preconditioning group, the neurological function score (1.90±0.31 vs. 2.50±0.52, P<0.05) and the degree of brain edema (3.60±0.52 vs. 7.70±0.94, P<0.001) were significantly lower than those in the cerebral ischemia group. Moreover, the expression of GRP78 in leptin-preconditioning group was significantly higher than that in ischemia group (48.69 ±5.06 vs. 35.78± 4.35, P<0.01), and the expression of CHOP was significantly lower than that of ischemia group (60.24 ±4.11 vs. 38.81±5.34, P<0.01). Conclusion Leptin can reduce the neurological deficit and may be associated with the up-reg-ulation of GRP78 protein, and down regulation of CHOP protein to weaken the endoplasmic reticulum stress caused by cerebral ischemia
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Objective To evaluate the effects of Xifeng Dingxuan granules on behavioral changes and brain energy metabo-lism on focal incomplete cerebral ischemia vertigo model rat. Methods Experimental rats were divided into normal control group, sham operation group, model group, flunarizine hydrochloride group(0.5 mg/kg), ginkgo leaf group(8 mg/kg)and Xifeng Dingxuan granule groups(0.27, 0.54 and 1.08 g/kg). The drugs were all administered intragastrically. During the experimental period, stepdown test was conducted to monitor the escape latency of rats from electrical stimulation, and the blood flows in right brain vestibular nucleus were measured. At the end of the experiment, the levels of the lactate (LAC), lactic acid dehydrogenase (LDH), superoxide dismutase(SOD)and malondialdehyde (MDA)in brain tissue were determined by colorimetry. Results 1. Compared with the normal control group, the escape latency of rats from electrical stimulation in model group was significantly prolonged (P<0.01). The escape latency was significantly reduced by the treatment of Xifeng Dingxuan granules (P<0.01), and the dosage of 0.54 g/kg was most effective. 2. Compared with the sham operation group, the blood flow of right brain vestibular nucleus in the model group was decreased (P<0.01). The decreased blood flow could be alleviated by the treatment of Xifeng Dingxuan granules and the dosage of 0.27 g/kg was most effective (P<0.01). 3. Compared with sham operation group, the contents of LAC and LDH in the right brain tissue were signifi-cantly increased in the model group (P<0.01). Compared with the model group, the contents of LAC and LDH were decreased signifi-cantly by the treatment of Xifeng Dingxuan granules with the dosage of 0.27 g/kg and 0.54 g/kg (P<0.01). 4. Compared with the sham operation group, the content of MDA and the activity of SOD in the right brain tissue were significantly increased in the model group (P<0.01)and could be alleviated by the treatment with Xifeng Dingxuan granules at each dose(P<0.01). Conclusion The results indicated that Xifeng Dingxuan granules could suppress the decrease of blood flow in vestibular nucleus, improve the brain energy me-tabolism and reduce the oxidative stress response in focal incomplete cerebral ischemia vertigo rat model, which implicated the possible therapeutic effect of Xifeng Dingxuan granules on the vertigo.
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O acidente vascular cerebral (AVC) é uma doença comum e uma das maiores causas de morte eincapacidade em todo o mundo. O acidente vascular cerebral isquêmico focal (AVCi) o corredevido a uma redução do aporte sanguíneo para uma região cerebral, levando ao decréscimo de oxigênio e glicose nos tecidos, induzindo a uma cascata de eventos, incluindo o estresse oxidativo e inflamação, que culminam com a morte neuronal e, com isso uma perda rápida da função neurológica. A Fisetina é um membro do subgrupo flavonol pertencente aos flavonoides,encontrado em diversas frutas e vegetais que apresentam propriedades antiinflamatórias e antioxidantes. O objetivo deste trabalho foi estudar os efeitos da Fisetina sobre o dano neuronal e memória, resposta inflamatória e sinaptogênese em camundongos submetidos ao modelo experimental de isquemia cerebral focal permanente (pMCAO). Os foram animais divididosentre os grupos falso-operados, tratados com veículo ou fisetina (FIS) na dose de 50 mg/kg,isquemiados tratados com veículo e isquemiados tratados com FIS nas doses de 10, 30, e 50mg/kg via oral, 3 horas depois da eletrocauterização da artéria cerebral média. O modelo deisquemia cerebral focal permanente foi comprovado através do aumento significativo da área de infarto e dos déficits sensório-motores nos animais isquemiados, observado através da coloração com TTC e da avaliação neurológica...
Stroke is a common disease and a major cause of death and disability worldwide. The focalischemic stroke (ischemic stroke) occurs due to a reduced blood supply to brain region,leading to the decrease of oxygen and glucose in tissues, inducing a cascade of eventsincluding oxidative stress and inflammation, culminating with neuronal death and thus a rapidloss of neurological function. Fisetin is a member of subgroup belonging to the flavonolflavonoid found in many fruits and vegetables that have anti-inflammatory and antioxidantproperties. The objective of this work was to study the effects of fisetin on neuronal damageand memory, inflammatory response and synaptogenesis in mice undergoing experimentalmodel of permanent focal cerebral ischemia (pMCAO). Were animals divided between thefalse-operated groups treated with vehicle or fisetin (SIF) at a dose of 50 mg / kg-ischemictreated with vehicle and-ischemic treated with FIS in doses of 10, 30, and 50 mg / kg po 3hours after the middle cerebral artery electrocautery. The permanent focal cerebral ischemiamodel was proven by the significant increase in infarct area and sensorimotor deficits inischemicanimals, observed by staining with TTC and neurological evaluation...
Subject(s)
Humans , Inflammation , Plants, MedicinalABSTRACT
O Acidente Vascular Encefálico (AVE) é definido como um quadro clínico de déficit neurológico que pode perdurar ou exceder as primeiras vinte e quatro horas do evento. A Organização Mundial de Saúde (OMS) revela que entre os anos de 2000 e 2011, o AVE apresentou-se como a segunda principal causa de óbitos em todo o mundo. Segundo o Ministério da Saúde, o AVE é a principal causa de morte no Brasil. É causado pela diminuição da perfusão sanguínea com depleção de oxigênio e glicose ao cérebro, causando redução dos níveis de ATP e predispondo a eventos como: excitotoxicidade glutamatérgica, influxo exacerbado de Ca++, estresse oxidativo, inflamação e apoptose, resultando em morte neuronal. O eriodictiol (3‟,4‟,5,7-tetrahidroxiflavanona) é um flavonóide encontrado na erva chinesa (Dracocephalum rupestre). Possui atividades anti-inflamatória, antioxidante e antiapoptótica já reportadas. O objetivo deste trabalho foi estudar os efeitos do eriodictiol sobre o dano neuronal, déficits de memória e resposta infamatória de camundongos submetidos à isquemia cerebral focal por oclusão permanente da artéria cerebral média (pMCAO). Os animais foram tratados oralmente com eriodictiol (1, 2 e 4 mg / kg) ou veículo (5% Tween 80 em salina 0,9%) 30 min antes, 2 horas depois da pMCAO e diariamente durante 4 dias. A pMCAO promoveu dano cerebral nos animais isquemiados, sendo esse comprovado, por meio da detecção do aumento significativo nas percentagens das áreas de infarto, pelos déficits sensório-motores observados e pela perda da viabilidade neuronal. O eriodictiol reduziu a área de infarto cerebral nas doses de 1, 2 e 4 mg/kg e preveniu os animais isquemiados dos déficits neurológicos 24h após pMCAO...
Stroke is defined as a clinical neurological deficit that may last or exceed the first twenty-four hours of the event. The World Health Organization (WHO) reveals that between 2000 and 2011, the Stroke was presented as the second leading cause of death worldwide. According to the Ministry of Health, stroke is the leading cause of death in Brazil. It is caused by decreased blood perfusion depleted of oxygen and glucose to the brain,causing ATP reduction levels and predisposing to events such as glutamatergic excitotoxicity, exacerbated influx of Ca++, oxidative stress, inflammation and apoptosis, resulting in neuronal death. The eriodictyol (3 ', 4', 5,7-tetrahydroxyflavanone) is a flavonoid found in the Chinese herb (Dracocephalum rupestre) having anti-inflammatory, antioxidant and anti-apoptotic effects previously reported. The objective of this study was to analyze the effects of eriodictyol on neuronal damage, memory deficits and inflammatory-response of mice subjected to focal cerebral ischemia by permanent meddle cerebral artery occlusion (pMCAO). The animals were treated orally with eriodictyol (1, 2 and 4 mg / kg) or vehicle (5% Tween 80 in saline 0,9%) 30 minutes before, 2 hours after the pMCAO and daily for 4 days. The promoted pMCAOischemic brain damage in animals, this being confirmed by means of detection of a significant increase in the percentage of infarcted areas, the observed sensorimotor deficits and loss of neuronal viability. The eriodictyol reduced the area of cerebral infarction in doses of 1, 2 and 4 mg / kg and prevented the animal-ischemic neurological deficits 24h post-pMCAO...
Subject(s)
Humans , Inflammation , Brain Ischemia , MemoryABSTRACT
Objective To investigate the effect of exercise preconditioning on the expression of nerve growth factor(NGF) and its receptor TrkA as well as learning-and-memory abilities in rats suffered from focal cerebral ischemia.Methods Thirty-six male SD rats were randomly divided into sham operation group (Sham-MCAO,n=12),focal cerebral ischemia-reperfusion group (MCAO,n=12) and exercise preconditioning + cerebral ischemia-reperfusion group (EX+MCAO,n=12).Rats in EX+MCAO group were placed in the treadmill device and accepted 4 weeks exercise training.Then method of middle cerebral artery occlusion was applied to prepare transient focal cerebral ischemia reperfusion model.Garcia's method was used to assess the neural function in rats.Western blotting was applied to test the expression of NGF and TrkA protein in the successfully established experimental MCAO rats.Morris water maze experiment was uti lized to test the learning-and-memory abilities of the rats.Results (1) Compared with Sham-MCAO group,the expression of NGF in rats' brain tissue was lower in MCAO group (cerebral ischemia 1h reperfusion 24h) (P＜0.05).The expression of NGF of EX+MCAO group was higher than that of MCAO group,but still lower than that of Sham-MCAO group (P＜0.05).(2)The expression of TrkA in rats' brain tissue was higher in MCAO group compared with Sham-MCAO group (P＜0.05).Compared with MCAO group,the expression of TrkA was even higher in EX+MCAO group (P＜0.05).(3)On the fifth day in the Morris water maze test,the latency of MCAO group was significantly longer than that of Sham-MCAO group((9.36± 1.18)s vs (4.86± 1.52) s,P＜0.05).However,compared with MCAO group,the latency in EX+MCAO group ((6.02± 1.04) s) was shorter,but still longer than Sham-MCAO group (P＜0.05).There was no significant difference among the three groups in the average swimming speed (P＞0.05).Conclusion Exercise preconditioning can up-regulate the expressions of NGF and TrkA protein,which can also improve the learning-and-memory abilities in rats suffered from focal cerebral ischemia reperfusion injury.
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@#Objective To investigate the effect of electroacupuncture (EA) at Quchi (LI11) and Zusanli (ST36) acupoints on rats with focal cerebral ischemia, and whether it was mediated by microRNA- 9 (miR- 9) regulating neural stem cells proliferation in subventricular zone. Methods Fifty-two Sprague-Dawley rats were randomly assigned into sham group (n=12), model group (n=12), EA group (n=12), EA+dimethylsulfoxide (DMSO) group (n=8) and EA+miR-9 mimics group (n=8). The middle cerebral artery occlusion model was induced. DMSO and miR-9 mimics were performed by intracerebroventricular injection 30 minutes before modeling. The EA group, EA+ DMSO group and EA+miR-9 mimics group were electroacupunctured at Quchi and Zusanli acupoints the next day after modeling. All the groups were intraperitoneally injected with bromodeoxyuridine (BrdU). The BrdU co-localized with Nestin was observed by immunofluorescence. The expression of miR-9 in subventricular zone was detected by real time qPCR. Results The neurological deficit score was lower (t=9.600, P=0.006), and the infarct volume was smaller (t=14.080, P=0.024) in the electroacupuncture group than in the model group. The expression of Nestin and BrdU co-localizated with Nestin increased; while the expression of miR-9 decreased in subventricular zone (P<0.05) in the electoacupuncture group. However, the expression of Nestin, BrdU and BrdU co-localizated with Nestin was lower in the EA+miR-9 mimics group than in the EA+ DMSO group. Conclusion Electroacupuncture at Quchi and Zusanli acupoints may promote the neural stem cells proliferation in subventricular zone by downregulating the miR-9 expression.
ABSTRACT
Objective To explore the effect of exercise training on learning and memory ability in rats with focal cerebral ischemia, and to analyze the changes of brain tissue structure of rats after exercise training through diffusion tensor imaging (DTI). Methods Twenty-four SPF male Sprague-Dawley rats were randomly divided into sham operation group (n=8), natural recovery group (n=8) and exercise training group (n=8). The left middle cerebral artery occlusion (MCAO) model was established. The exercise training group received running wheel training 24 hours after modeling, for 14 days. All groups were tested by the Morris water maze 15 days after modeling. The latency in the navigation experiment, as well as the first latency, boundary swimming time ratio, the boundary swimming distance ratio, the average speed and the swimming path in the space exploration experiment were recorded. Four rats with similar Longa scores in each group received rou-tine magnetic resonance imaging and DTI scanning, the fractional anisotropy (FA), axial diffusivity (λ‖), and radial diffusivity (λ⊥) of isch-emic cortex and hippocampal lesion and contralateral side were measured. Results In the navigation experiment, the latency of three groups showed a downward trend along with training days (P0.05), while it was shorter in the exercise train-ing group than in the natural recovery group in the same time (P2.627, P2.521, P0.05). The swimming paths in the exercise training group and the sham operation group were better than that of the natural recovery group. The FA and rFA in the left cortical area were higher in the sham operation group than in the exercise training group and the natural recovery group (P0.05). There was no significant difference in the FA in the right cortical area among three groups (F=0.532, P=0.607). Theλ⊥,λ‖, rλ‖and rλ⊥in the left cortical area were lower in the sham opera-tion group than in the natural recovery group (P0.05). There was no significant difference in theλ⊥andλ‖in the right cortical area among three groups (F0.05). There was no significant difference in the FA,λ⊥,λ‖and rFA, rλ⊥and rλ‖in the bilateral hippo-campal interest area among three groups (F0.05). The rFA, rλ‖, rλ⊥and leftλ⊥ were correlated with the latency in the space ex-ploration experiment in the Morris water maze test (P<0.05), in which the correlation coefficient of rλ⊥was the highest (r=0.761, P<0.01). Conclusion Proper exercise training can improve the learning and memory ability of rats with focal cerebral ischemia, and can promote the repair of nerve fiber damage and reduce the vascular edema. In addition, the rFA, rλ‖, rλ⊥andλ⊥of ischemic cortex may be predictors of cognitive function recovery in rats after focal cerebral ischemia, especially rλ⊥.