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BACKGROUND:Heparinase can induce syndecan-1 shedding from tumor cells and macrophage motion may correlate with biosynthesis regulation of heparan sulfate proteoglycan.OBJECTIVE:To investigate the effects of heparinase Ⅰ on syndecan-1 and extracelluar signal regulated kinase 2(ERK2)in human umbilical vein endothelial cells(HUVECS)with hypoxia/reoxygenation injury.METHODS:heparinase Ⅰ-precultured HUVECS were treated with hypoxia/reoxygenation.Immunohistochemistry staining,RT-PCR and western blot were applied to detect HUVECS syndecan-1 and ERK2 expression.RESULTS AND CONCLUSION:Expression of syndecan-1 and ERK2 was increased in HUVECS following hypoxia/reoxygenation treatment.Heparinase Ⅰ significantly upregulated the expression of syndecan-1 and ERK2 in HUVECS with hypoxia/reoxygenatiOn treatment.Syndecan-1 and ERK2 expression was positively related.Results show that syndecan-1 and ERK2 participate the pathophysiology of HUVECs hypoxia/reoxygenation injury Heparinase Ⅰ influences ERK2 expression by regulating syndecan-1.
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There are a number of serum biomarkers related with the process of the pathogenesis,destabilization and rupture of the atherosclerotic plaque.And thus,it is fairly important in clinical practice to identify vulnerable plaque and predict plaque rupture by detecting the expression of the serum biomarkers.This review aims at giving an overview on recent emerging biomarkers that are related to vulnerable plaque.
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Subarachnoid hemorrhage (SAH) is a disease with high disability and mortality rate.It is still lack of effective treatment means in clinical practice.Studies in recent years have found that early brain injury may be the primary causes that result in higher mortality and poor prognosis in patients with SAH.This article mainly reviews the animal models and pathogenesis of early brain injury after SAH.
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BACKGROUND: Changes of physiological structure, changes of phenotype and first basic excision are all the changes of gene expression. The technique of DNA microarray is a new method to filtrate target genes fleetly and largely by using the theory of base-partnershin, which can holistically and magnificently study the expression and function of organics genes. OBJECTIVE: To study early differential expression genes of rats with cerebral hemorrhage with DNA microarray and establish academic foundation for exploring mechanism of cerebral hemorrhage.DESIGN: Randomized controlled research.SETTING: Department of Neurology, Affiliated Hospital of North Sichuan Medical College. MATERIALS: The experiment was conducted at the Affiliated Hospital of North Sichuan Medical College from October 2002 to December 2003. Twenty Wistar rats, of either gender, with body mass of 220-260 g, without special pathogen, provided by Experimental Animal Center of Chongqing University of Medical Sciences, were selected and randomly divided into control group and cerebral hemorrhage group, with 10 in each group. METHODS: Animal models with cute cerebral hemorrhage of rats were established with type Ⅶ collagenase tridimensional localization method,and 4 hours later tissues around hematom and normal cerebral tissue at the same part were detected with gene chip. Fluorescent signal was scanned with scanning apparatus and analyzed with computer. Result of genic expressive pattern was researched with reverse transcriptase-polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURES: Result of gene chip in cerebral tissue of rats and result of RT-PCR.RESULTS: Four hours after acute cerebral hemorrhage, 129 differential expression genes were screened out, in which there were 114 up-regnlation genes and 15 down-regulation genes. Those genes were mostly related to the following aspects: stress, immunological response, apoptosis, energy metabolism and signal transmitting. Genes related with inflammatory impairment were mostly obvious. The result of RT-PCR suggested that the level of genic expression was as the same as the result of Cdna chip, which indicated that genic expressive pattern based on gene chip had great reliability.CONCLUSION: Early cerebral hemorrhage has many differential expression genes, which can play an important role in hemorrhagic brain damage.
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Objective To explore the mechanism of early-onset sub-clinical seizures following acute cerebral infarction. Methods Right middle cerebral artery occlusion (MCAO) rats models were made by threads methods. Sub-clinical seizures were detected with recording apparatus at the same time. Glial glutamate transporter-1 (GLT-1) were detected by immunohistochemical method in rats hippocampus. Results Sub-clinical seizures occurred in 27.4% rats following MCAO. The GLT-1 expressions in CA_1 and CA_3 regions were lower in sub-clinical seizure group[(344.5?35.0)?m~2 and (360.4?13.5)?m~2 respectively] than those in the controls[(447.0?22.8)?m~2 in CA_1 region and (402.3?28.5)?m~2 in CA_3 region]. But there were not significant differences of GLT-1 immunoreactivities in dentate gyrus between the two groups above. Conclusion Early-onset sub-clinical seizures occur following the acute MCAO in rats, which should be related to the decreased expression of GLT-1 in CA_1 and CA_3 of hippocampus.
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BACKGROUND: The incidence of cognition disturbance after cerebral infarction is about 20% -30% and effective drugs for its prevention and treatment are anticipated.OBJECTIVE: To investigate the effect of nicergoline on cognition disturbance after cerebral infarction and explore its mechanism.DESIGN: Randomized controlled trial based on patients.SETTING: Neurological department in a medical university.PARTICIPANTS: A total of 60 patients admitted to the Neurological Department of the Second Hospital Affiliated to Chongqing Medical University for cerebral infarction during October 1999 and April 2001 were recruited in this study, and randomly divided into two groups, nicergoline treatment group and control group with 30 in each.METHODS: Mini-mental state examination(MMSE) score was evaluated and cerebral blood flow was determined with transcranial Doppler' s ultrasonography within one week after admission and three months after admission, respectively, and data were analyzed with SPSS software.MAIN OUTCOME MEASURES: MMSE score and velocity of blood flow in treatment and control groups.RESULTS: MMSE score in memory, calculation and recollection decreased significantly[ (1.2 ± 1.3), (2. 2 ± 2. 1) and(1.0 ± 1.7), respectively] in control group but did not change much[ (3.9 ± 1.4), (4. 4 ± 1.9) and(4.0 ± 1.6) ]in treatment group. The velocity of blood flow in control group decreased apparently, while it increased in treatment group[(58.31 ±10. 15) and(65.79 ±9.74) cm/s in the right middle cerebral artery].CONCLUSION: Nicergoline can prevent and treat vascular cognition disturbance, and improvement of blood supply may be one of the mechanisms.
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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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0.05). The expression of GFP was located around the ventricle and persisted for a long time. Conclusion The fluorescence of GFP is stable and persistent and the GFP has no negative effects on the NSCs-GFP. It is an ideal maker of neural stem cells and could be used for the study of NSCs transplantation.
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AIM: To investigate the effect of hirudo and earthworm liquor extract on the expression of syndecan-1 in focal cerebral ischemia reperfusion rats and the relationship between syndecan-1 expression and cellists underlying antiinflammatory mechanism. METHODS: The MCAO models of rats were built with the intraluminal filament occlusion. Rats' brains were cut at the levels of the hippocampus as the templates. Immunohistochemistry staining and HE staining were used to facilitate the observation of the distribution and the quantities of cells with expression of syndecan-1 and the pathological change of MCAO ischemia 2 h reperfusion 4, 24, 72 h and 7 d with hirudo and earthworm liquor extract or saline treatment, respectively. RESULTS: Hirudo and earthworm liquor extract could upregulate the expression of syndecan-1 on ischemia/ reperfusion in rats' brains, especially at 72 h. The numbers of syndecan-1 cells got peak, hirudo and earthworm extract liquor could downregulate polynucleation inflammatory cells at 24 and 72 h. The expression of inflammatory cells in both hirudo and earthworm liquor extract group and saline group at 4 h was not significant. Hirudo and earthworm extract liquor downregulated the monocytic inflammation cells infiltration at 7 d. CONCLUSION: Hirudo and earthworm liquor extract can upregulate the expression of syndecan-1 on ischemia reperfusion in rats' brains. The upregulation of syndecan-1 can decrease inflammatory cell infiltrate.
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Objective To investigate the migration pathway and feature of neuronal precursors in normal adult rats and provide theory and experiment basis for the neuronal migration under pathological condition. Methods The adult rat brains were cut into 20 ?m coronal and sagittal sections on a freezing microtome. Immunohistochemistry was applied to observe the migration pathway and feature of DCX-expressing cells. Results There were two migration pathways with the neuronal precursors in normal adult rats. One was the rostral migratory stream (RMS) from the subventricular zone to the olfactory bulb, another appeared to travel in a chain along the interface between cortex and corpus callosum. The DCX-positive cells in the RMS had the fusiform somata with a single leading process and the process orientated to the olfactory bulb, while the DCX-positive cells around the corpus callosum had similarly round somata and the size, number and orientation of process were of diversity.Conclusion The study of neuronal precursors migrating not only contributes to identify the migration mechanisms, but also contributes to the control of neuronal migration and designs some effective therapy strategies.
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Objective To explore the pathogenic mechanisms of intractable epilepsy by searching for the differential cell signal transduction associated genes expression in intractable and non intractable epilepsy rat brain using cDNA microarray Methods Intractable epilepsy and non intractable epilepsy rat model were build The total RNAs were isolated from the brain tissues Both mRNAs from the brains of the intractable and non intractable epilepsy rats were reversely transcribed to the cDNA with the incorporation of fluorescent dUTP to prepare the hybridization probes The PCR products of 4 096 human genes were spotted on a chemical material coated glass plates in array The mixed probes were then hybridized to the cDNA microarray After high stringent washing, the cDNA microarray was scanned for the fluorescent signals and showed differences between 2 tissues Results Among the 4 096 target genes, 29 genes associated with cell signal transduction differentially expressed were identified, 10 were up regulated(34 48%) and 19 down regulated(65 52%) Conclusion cDNA microarray technology is an effective technique in screening the differentially expressed genes between intractable and non intractable epilepsy rat brain Disturbances of cell signal transduction play a role in the pathogenic mechanism of intractable epilepsy
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Objective To observe the changes of the content of ATP,lactate and the activity of phosphofructokinase(PFK) in perihemotoma region in rabbit brain after intracerebral hemorrhage. Methods(The rabbits) were divided into 3 groups: normal group(N),hemorrhage group (H) and the sham group(S). The H and S groups were subdivided into 1 h, 6 h, 12 h, 24 h, 48 h and 72 h groups. A model of cerebral hemorrhage in rabbit with autologous blood infusion was set. The contents of ATP, lactate and water in perihemotoma region were measured and the metabolite concentration in edematous brain regions were corrected for dilution. The activity of phosphofructokinase was also determined.Results There was obvious edema in perihemotoma region at 1 hour postinfusion and getting more serious at 72 hours. ATP was moderately decreased at 1 hour, and remained in a similar level until 12 hours. There appeared another evident decrease in 24 hours [(13.29?2.92) ?g/g, about 58% of N group], and no obvious changes from 24 to 72 hours. The content of lactate increased in 1 hour and reached the peak at 12 hours [(21.01?0.18) ?mol/g]. Until 72 hours , the level of lactate [(12.89?0.25) ?mol/g] in hemorrhage group reach higher than in the normal and sham group. The activity of phosphofructokinase was decreased at 1 hour [(3.98?0.02) U/mg] and remained in a decreasing tendency to 72 hours. Conclusion The failure of energy metabolism occurs in 24 hours postinfusion,coming late somewhat to the brain edema. The result might be related to the changes of some enzymes, maybe a key role in energy metabolism.
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Objective To study the effects of hirudo extract liquor(HEL) on the expressions of HSP70 and TGF?-1 in intracerebral perihematoma tissues of rats.Methods We established the experimental ICH models in Wistar rats by stereotaxical injecting quantitative collagenase(0.7 U collagenaseⅦ) into their left caudate nuclei.The rats continued to be treated with HEL(treatment group) or normal saline(control group) through intravenous injection by vena caudalis and the scores of neurologic impairment in two groups were evaluated every day.The slices of these samples at 3rd,6th and 10th day were stained by immunohistochemistry and the positive cells of HSP70 and TGF?-1 were counted by image analysis system,respectively.Results The scores of neurologic impairment in two groups were remarkably reduced with time going((P
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Objective To investigate the effect of purified haemadipsa yanyuanensis injection on promoting intracerebral hematoma in rats and its possible mechanism.Methods We set up the experimental intracerebral hemorrhage (ICH) model in rats by stereotaxically injecting quantitative collagenase into their left caudate nucleuses.The effects of haemadipsa yanyuannesis injection on hematoma volume,neurological function recovery,brain water content(BWC),as well as histopathological changes were observed. BWC was calculated by weighing method,local capillaries were observed by micrangium perfusion.Results The intracerebral hematoma of the rats was reduced significantly( P
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Objective:To explore protective action of ultramicro-powder of Rhizoma Gastrodiae on nerves in the rat of Cerebral ischemia- reperfusion injury.Methods:The local ischemia-reperfusion injury at model was established by cerebral ischemia for 2 hours and reperfusion for 24 hours.HE staining,2,3,5-triphenytetrazolium(TTC)staining,immunohistochemical methods were respectively used to investigate pathological changes of brain slices,the size of cerebral infarction and nervous cell apoptotic relative proteins Bcl-2,Bax expression after treatment with ultramicro-powder of Rhizoma Gastrodiae.Results:(1)Ultramicro-powder of Rhizoma Gastrodiae could reduce the size of cerebral infarction.When the low,middle and high dose groups were compared with the ischemia group there were significant differences(P
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AIM: To investigate the effects of Dihuang Yizhi Extract(DHYZE) on learning-memory ability and the central cholinergic system of the rats with Alzheimer's disease(AD) and to explore the possible mechanism of action. METHODS: Aggregated A?25-35 was injected into the right hippocampus of the rats to make experimental rat model of AD.The behavioral abnormalities were investigated by shuttle box.The contents of acetylcholine(Ach)、cholinesterase(ChE) activity、cyclic AMP response element-binding protein(CREB) and phosphorylated CREB serine 133(pCREB Ser133) in hippocampus were measured. RESULTS: DHYZE could markedly improve the function of learning and memory of rats in AD model in a dose-dependent manner.The contents of Ach and AchE activity in hippocampaus increased obviously in DHYZE medium dose group and high dose group compared with AD group.Such promotion was dose-dependent.The contents of pCREB Ser133 in hippocampaus increased obviously in DHYZE high dose group compared with AD group. CONCLUSION: The results indicate DHYZE could improve the ability of spatial learning and memory in AD rats.The mechanism might be associated with improving the impairment of the central cholinergic neurons induced by A?25-35 and activating CREB signal pathway in hippocampus of AD rats.
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Objective To observe the effect and safety of buflomedil hydrochloride injection to intra cerebral hemorrhage in rats. Methods We established the experimental intracerebral hemorrhage (ICH) model in rats by stereotactic injecting quantitative collagenase into their left caudate nucleuses.The effects of buflomedil hydrochloride injection on hematoma volume,the score of neurological function deficit signs, as well as histopathological changes were observed. Local capillaries were observed by micrangium perfusion.Results 5 days after buflomedil hydrochloride injection might alleviate Wister rats' neurological function deficit signs, 86% rats from Grade Ⅲ to Grade Ⅰ, 14% rats from Grade Ⅲ to Grade 0( P
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Objective To study the effect of sodium ferulate (SF) on the expressions of nuclear factor-?B (NF-?B) and inhibitory ?B? (I?B?) in rat brain microvascular endothelial cells (BMEC) injured by hypoxia. Methods Brain microvascular endothelial cells from Wistar rat cerebral cortex were isolated and cultured, and then cultivated in 95%N_2 and 5% CO_2 for 12 h to induce hypoxia injury. The cells were divided into normal group, hypoxia group, and SF group. BMEC activity was assayed by MTT assay. Endothelin-1(ET-1) concentration was evaluated by radioimmunoassay.The expression of NF-?B and I?B? of BMEC were assessed by immunocytochemistry. Results The content of ET-1 in BMEC media was increased after hypoxia, while sodium ferulate (100 ?g/ml) significantly decreased the content compared with hypoxia group. Immunocytochemistry indicated I?B? expression were significantly decreased in hypoxia BMEC in consistent with NF-?B expression. Conclusion Sodium ferulate may significantly reduce NF-?B of hypoxia BMEC and nuclear translocation, and increase I?B? expression and BMEC activity. It is a potent inhibitor of NF-?B in endothelial cells, which might explain its beneficial effect on injured BMEC by hypoxia.
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Objective To investigate the effect of hypoxia-inducible factor-1? gene on the proliferation and differentiation of neural stem cells after focal cerebral ischemia in rats,and to explore the mechanism of the effect. Methods Middle cerebral artery occlusion(MCAO) and reperfusion models were established and divided into sham group,NS group,AD group and Ad-HIF-l? group.NS,AD and Ad-HIF-l? were injected into the ischemic ventricle respectively.The mNSS was evaluated the expression of EPO was observed,and the number of BrdU positive cells in subventricular zone and that of BrdU/NF200,BrdU/GFAP double labeled cells in cortex were calculated by immumofluorescence method.Results The mNSS were statistically different between Ad-HIF-l? group and the other three groups;the expression of EPO was higher in Ad-HIF-l? group;the number of BrdU positive cells increased obviously in Ad-HIF-l? group;the cellular rebirth and differentiation demonstrated that there existed a significant difference(P