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【Objective】 To observe the effect of puerarin on the concentration of Ca2+ and the expression of brain derived neurotrophic factor (BDNF) in hippocampal neurons of vascular dementia (VD) rats so as to explore the mechanism of puerarin in protecting nerve cells. 【Methods】 Male SD rats were randomly divided into sham operation group, model group, and puerarin intervention group. The vascular dementia model was established by ligating bilateral common carotid arteries at intervals of 3 days. Two weeks after the operation, the learning and memory abilities of the rats were evaluated by Morris water maze, and the expression of BDNF in the hippocampus of the rats was detected by immunohistochemistry and Western blotting. The mean fluorescence intensity was measured by flow cytometry to represent the intracellular free Ca2+ concentration. 【Results】 In the puerarin intervention group, the rats’ escape latency in Morris water maze was significantly shortened, the expression of BDNF in the hippocampus was significantly increased, and the concentration of Ca2+ in hippocampal neurons was decreased. Compared with the model group, the difference was statistically significant (all P<0.05). 【Conclusion】 Puerarin has neuroprotective effect on VD rats, and its mechanism may be related to the decrease of Ca2+ concentration in hippocampal neurons and the up-regulation of BDNF expression.
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As terminally differentiated cells, neurons undergo aging with specific patterns.Understanding the characteristics of neural cell senescence and associated aging models is helpful to select appropriate models for the study of nervous system senescence.
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OBJECTIVE@#To study the protective effect of enhanced peroxisome proliferator activated receptor γ (PPARγ) pathway against apoptosis of long-term cultured primary nerve cells.@*METHODS@#A natural aging model was established in primary rat nerve cells by long-term culture for 22 days. The cells were divided into control group, 0.1, 1.0, 5.0, and 10 μmol/L GW9662 intervention groups, and 0.1, 1.0, 5.0, and 10 μmol/L pioglitazone intervention groups. The cell viability was assessed using MTT assay and the cell morphological changes were observed after the treatments to determine the optimal concentrations of GW9662 and pioglitazone. Double immunofluorescence labeling and flow cytometry were used to observe the changes in the number of viable cells and cell apoptosis following the treatments; immunocytochemical staining was used to assess the changes in the anti-oxidation ability of the treated cells.@*RESULTS@#The optimal concentrations of GW9662 and pioglitazone determined based on the cell viability and morphological changes were both 1 μmol/L. Compared with the control group, GW9662 treatment significantly lowered while pioglitazone significantly increased the total cell number and nerve cell counts ( < 0.05), and nerve cells in the cell cultures maintained a constant ratio at about 80% in all the groups ( > 0.05). GW9662 significantly enhanced while pioglitazone significantly lowered the cell apoptosis rates compared with the control group ( < 0.05). GW9662 obviously lowered SOD activity and GSH content in G group ( < 0.05) and increased MDA content in the cells ( < 0.05), and pioglitazone resulted in reverse changes in SOD, GSH and MDA contents in the cells ( < 0.05).@*CONCLUSIONS@#Activation of PPARγ pathway protects long-term cultured primary nerve cells by enhancing cellular anti-oxidant capacity and reducing cell apoptosis, suggesting a potential strategy for anti-aging treatment of the nervous system through intervention of the PPARγ pathway.
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Animals , Rats , Anilides , Pharmacology , Apoptosis , Cell Proliferation , Cell Survival , Cells, Cultured , Cellular Senescence , Physiology , Neurons , Cell Biology , PPAR gamma , Metabolism , Pioglitazone , PharmacologyABSTRACT
Objective@#To investigate the clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis, and to explore immune therapeutic strategies for targeted therapy for liver cirrhosis.@*Methods@#In vitro peripheral blood mononucleated cells (PBMCs) were collected by centrifugation. CD3-BV500 and CD8-PerCP-Cy5.5 staining was performed for these cells. IFNγ-PE-Cy7, IL-17a-APC, IL-22-PE, or the corresponding isotype control was added, and then PBMCs were fixed with 1% polyoxymethylene after being washed once by permeabilization-wash buffer. Flowjo software was used for the analysis of T lymphocyte subsets and cytokines. Th1 (CD4+IFNγ+), Th17 (CD4+IL-17a+), Th22 (CD4+IL-22+), Tc1 (CD8+IFNγ+), Tc17 (CD8+IL-17a+), and Tc22 (CD8+IL-22+) subsets were defined and the secretions of interferon-γ (IFN-γ), interleukin-17a (IL-17a), and interleukin-22 (IL-22) were measured for all subsets. LX-2 cells were cultured in a serum-free medium and different concentrations of recombinant human IL-22 protein (25, 50, 100 ng/ml) were added; 24 hours later, the activation marker α-smooth muscle actin (α-SMA) was used to measure LX-2 activation. Fetal bovine serum with a volume fraction of 10% was used as a positive control. Enzyme-linked immunosorbent assay (chemiluminescence) was used to measure the concentrations of hyaluronic acid, type III precollagen, and type IV collagen in supernatant. A one-way analysis of variance, the non-parametric Mann-Whitney U test, and the non-parametric Kruskal-wallis H test were used for statistical analysis based on data type.@*Results@#Compared with the health control group, the liver cirrhosis groups with various causes had significant increases in peripheral Tc1, Th17, and Th22 cells. The percentage of Th17 cells in the liver cirrhosis group was 1.64 times that in the control group (4.25%±2.45% vs 2.59%±1.36%, P < 0.05), and the mean percentage of Th22 cells in the liver cirrhosis group was 2.18 times that in the control group (4.17%±2.55% vs 1.31%±0.64%, P < 0.05). The percentages of Th17 (5.89%±3.44%) and Th22 cells (5.32%±3.67%) in the patients with alcoholic cirrhosis were 1.27 and 3.06 times those in the control group (P < 0.05). The patients with alcoholic cirrhosis had a significant increase in Th22 cells. The patients with different types of liver cirrhosis had a significant reduction in the ratio between anti-fibrotic and pro-fibrotic factors (Th1/Th22), which was positively correlated with the severity of liver cirrhosis and was a common immunological feature of liver cirrhosis with different causes. In addition, IL-22 activated hepatic stellate cells and promoted the production of collagen.@*Conclusion@#The imbalance between anti-fibrotic and pro-fibrotic factors (Th1/Th22) is a common feature of the progression of liver fibrosis with various causes and may contribute to the progression of liver fibrosis.
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OBJECTIVE@#To investigate the expression of inflammatory molecule CD40 in the pallium and hippocampus of rats after status epilepticus (SE). @*METHODS@#The expression of CD40 in the pallium, the different areas of hippocampus and the different cells from the lithium-pilocarpine epileptic rats at different time points were examined by immunohistochemistry and double-immunofluorescent labeling. @*RESULTS@#After SE, CD40 expression was obviously inhibited, especially in hippocampus. CD40 was mainly expressed in the activated microglia. CD40 positive cells reached a peak at the 3rd day and returned to a slightly higher level at the 7th day after SE compared with the level before SE. @*CONCLUSION@#Elevation of CD40 expression in the activated microglia can promote inflammatory injury of rat's hippocampus, suggesting that CD40 induced-signal pathway is involved in inflammatory injury in the hippocampus after SE.
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Animals , Rats , CD40 Antigens , Metabolism , Epilepsy , Hippocampus , Metabolism , Immunohistochemistry , Lithium , Microglia , Metabolism , Pilocarpine , Rats, Sprague-Dawley , Status EpilepticusABSTRACT
Objective To investigate the safety, efficacy and key points of technology of endovascular embolization for ruptured wide-necked aneurysms of anterior communicating arteries. Methods The clinical, DSA imaging, interventional treatment and follow-up data of 35 patients with ruptured wide-neck aneurysms of anterior communicating arteries were analyzed retrospectively. Results Immediate postoperative angiography of the 35 patients found 100% occlusion were achieved in 29 (82.9%), 90% occlusion were achieved in 5 (14.3%), and 80%occlusion was achieved in 1 (2.8%). One patient had occlusion in ipsilateral anterior cerebral artery , whose blood vessel was patent after thrombosis. One patient had intraoperative aneurysm rupture. One patient had cerebral infaraction of anterior cerebral artery after the operation. Clinical follow-up was made from 6 to 60 months , and no aneurysms ruptured was found. 21 patients were followed up for 6 to 60 months with DSA. Two of them experienced recurrence, and they were not treated with supplementary packing. Conclusion Endovascular embolization for ruptured wide-necked aneurysms of anterior communicating arteries is more difficult , but it is safe and effective. Flexible choosing of various kinds of embolism technique and designing the most optimal embolism treatment plan are the keys to the improvement of embolization effect.
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Objective To investigate the feasibility,efficacy and key points of individually designed endovascular embolization for ruptured tiny aneurysms of anterior communicating arteries. Methods The clinical,DSA imaging,interventional treatment and follow-up data of 21 patients with ruptured tiny aneurysms (21 aneurysms)of anterior communicating arteries from March 2009 to March 2014 were analyzed retrospectively. Thirteen of them were treated with coil embolization only,6 were embolized with microcatheter-assisted technique,and 2 were embolized with balloon-assisted technique. Results (1)One patient was failed to embolize because of technical reason. Immediate postoperative angiography found that in the other 20 patients:14 were packed densely,6 had residual aneurysm necks. (2)Intraoperative complications:One patient had acute occlusion of ipsilateral anterior cerebral artery,the blood vessel was patent after thrombolytic method;2 patients had intraoperative ruptured aneurysm. (3)The modified Rankin scale (mRS)scores of 20 patients with successful embolization at discharge:0-1 in 14 cases,2 in 4 cases, and 3-4 in 2 cases. (4)Follow-up study:20 patients were followed up for 12 months after discharge. The mRS scores:0-1 in 18 cases,2 in 1 case,and 3-4 in 1 case. Clinical follow-up for 6 to 60 months,no aneurysm ruptured. Fifteen patients were followed up for 6 to 60 months with DSA,one of them recurred,and he was treated with supplementary dense packing. Conclusion Endovascular embolization for ruptured tiny aneurysms of anterior communicating arteries is difficult,but it is feasible and effective. The proficient surgical skill,individualized surgical design and appropriate embolism are the keys to improve the embolization effect.
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Objective:To observe the distribution of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in different brain regions in aged rats and determine the role of VEGF and MVD in the aging process of the nervous system. Methods:We observed the expression of VEGF and MVD in different parts of rat brain in the 3- month group and 30-month group with immunohistochemical technique. Results:Compared with the 3-month group, the 30-month group showed fewer VEGF-positive cells and MVD in the brain (P<0.01), and the number varied signiifcantly in different brain regions(P<0.01). The motor cortex region contained more VEGF-positive cells and MVD than the hippocampus and cerebellum. Conclusion:VEGF-positive cells and MVD are decreased in every brain region of aged rats, and the motor cortex region contains more positive cells, suggesting exogenous VEGF may enhance the formation of microvessels and delay the aging of the nervous system.
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The function of erythropoietin (EPO) is recognized as a stimulator for proliferation of red blood cell (RBC), however,recent studies have showed that EPO and EPO-R are widely distributed in nervous system, which indicates that it may also have important functions in nervous system. Studies proved its neuroprotective effects, especially in ischemic-hypoxic nerve tissues. These effects are mainly activated through several signal transduction pathway downstream and multiple mechanisms are involved. As a neuroprotective factor, EPO has been investigated in the clinical studies, which may lead to the clinical application in the future.
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Humans , Erythropoietin , Metabolism , Physiology , Neurophysiology , Neuroprotective Agents , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To study the effect of erythropoietin (EPO) on the activities of antioxidant enzymes, namely catalase (CAT) and glutathione peroxidase (GSH-Px) in the brain tissues of aged rats.</p><p><b>METHODS</b>Thirty SD rats were randomly divided into normal control, aging model, and recombinant human erythropoietin (rhEPO) treatment groups (n=10). Morris water maze was used to compare the behavioral indexes. The rats were then sacrificed to observe Nissl bodies in the hippocampal neurons with Nissl staining and test the activities of CAT and GSH-Px in the brain tissues.</p><p><b>RESULTS</b>Compared with the control group, the aging rats showed significantly deteriorated learning and memory abilities (P<0.05), which were improved obviously by rhEPO treatment (P<0.05). The number of Nissl bodies in the neurons was reduced in the aging rats compared with that in the control group, and rhEPO treatment increased the number of Nissle bodies but failed to restore the control level. The aging rats also showed significantly lowered activities of CAT and GSH-Px in the brain tissue (P<0.05), which were increased significantly after rhEPO treatment (P<0.05).</p><p><b>CONCLUSION</b>EPO can enhance the activities of the antioxidant enzymes in the brain tissues of aged rats to increase the antioxidant capacity and produces an anti-aging effect.</p>
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Animals , Male , Rats , Aging , Brain , Catalase , Metabolism , Epoetin Alfa , Erythropoietin , Pharmacology , Glutathione Peroxidase , Metabolism , Learning , Memory , Nissl Bodies , Rats, Sprague-Dawley , Recombinant Proteins , PharmacologyABSTRACT
OBJECTIVE@#To explore the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and erythropoietin in the hippocampus of aging rats, and to investigate the role of HIF-1alpha and erythropoietin in the aging of nervous system.@*METHODS@#The expression of Nissl body, HIF-1alpha, and erythropoietin in the CA1 region of the hippocampus in different months was observed by Nissl staining and immunohistochemical technique.@*RESULTS@#Nerve cells became bigger and appeared sparse, and the Nissl bodies decreased with age. HIF-1alpha positive cells increased significantly with age in the CA1 region of the hippocampus (P<0.05). The expression of erythropoietin presented a parabola with aging in the CA1 region of the hippocampus. The increase from 3 to 18 months and the reduction from 18 to 30 months of erythropoietin positive cells had statistical significance (both P<0.05).@*CONCLUSION@#HIF-1alpha and erythropoietin are parallelly incremental before middle age, and are separated after middle age, suggesting decreased activity of HIF-1alpha and recession of protein synthesis function may be the main reasons for decreased expression of erythropoietin in the brain during aging. Strengthened endogenous HIF-1alpha activity and supply of exogenous erythropoietin may delay the aging of the nervous system.
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Animals , Male , Rats , Aging , Metabolism , Erythropoietin , Metabolism , Hippocampus , Metabolism , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Cognitive impairments are often accompanied in patients with silent cerebral infarction (SCI) and depression, and there is still no reliable objective assessing method for the evaluation.OBJECTIVE: The purpose of this study was to probe into the value of auditory P300 in detecting the cognitive impairment in SCI patients with depression.DESIGN: A golden standard control study.SETTING: Department of Neurology, Xi 'an Central Hospital; Department of Neurology, the Second Hospital of Xi' an Jiao Tong University.PARTICIPANTS: Thirty-eight SCI patients were selected from the Outpatient Department of Neurology, the Second Hospital of Xi' an Jiao Tong University between January 2002 to May 2003, including 10 got dizziness,11 got poor concentration, 8 got headache, 5 got numbness of extremities and 4 got syncope. Among them, 26 were detected by CT and 12 by MRI.The patients'aged 45 to 63 years with mean age of (57.3±5.1) years, including 20 males and 18 females.METHODS: The existence of depressive symptoms was measured with the 17-item Hamilton depression scale (HAMD). In this scale, the total score ranged from 0 to 52, with higher score indicating more severe depressive symptoms, and the patient was considered as having depression if the HAMD score was ≥ 9. HAMD tests were administered by two psychiatrists,who were experienced in psychiatric disorders in stroke and other somatic diseases, and the two psychiatrists had a better coincidence (Kappa=0.86 -0.91). The auditory event related potential was detected with MYTO serial cerebra induced potential meter, while lying in a bed placed in a sound-attenuated room. Auditory stimuli were delivered binaurally through headphones. The subject was required to distinguish between the tones by noting the occurrence of the target and not to respond to the standard. All patients underwent a routine experimental test at first, and then a normal test was performed to obtain a better coincidence. Mini-mental state examination (MMSE) was conducted for the 38 patients by specialized training neurologist to assess the cognitive impairment, in which the total score ranged from 0 to 30, with lower score indicating greater impairment. The criteria of intellectual deterioration was defined on the basis of educational level:MMSE score of 17 for illiterate, 20 for primary school and 24 for middle school and above.MAIN OUTCOME MEASURES: The score of MMSE, latent period of P300 wave and amplitude of P300 wave were mainly observed.RESULTS: All the 38 cases were involved in the final statistical analyhave depressive symptoms (47%, depression group) and 20 had no depresindexes and score of MMSE between the SCI patients with and without depression: As compared with the SCI patients without depression, the P300 latent period was obviously prolonged, the P300 amplitude and MMSE score were markedly decreased in the SCI patients with depression [(383.3±31.1), (347.2±37.3) ms; (5.6±0.7), (9.9±1.6) μV; (15.2±1.1),and P300 indexes: In the SCI patients with depression, the P300 latent period had significant negative correlation with the MMSE score (r=-0.549, P ＜ 0.05), the P300 amplitude had significant positive correlation with the MMSE score (r =0.525, P ＜ 0.05). However, there was no correlation between the latent period and amplitude of P300 and the MMSE score in the SCI patients without depression (r=-0.349 to 0.065, P ＞ 0.05).CONCLUSION: Depression and cognitive impairments may have the same pathophysiological basis in SCI patients. P300 can be used as a referential and objective method to analyze the cognitive function in SCI patients with depression.
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Objective To study the changes of serum creatase and its clinical significance in patients with periodic paralysis.Methods The serum creatine phosphatase (CPK),lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were measured by means of speed rate method in 103 patients of periodic paralysis and 35 healthy persons as the control group. The relationship between increased serum creatase levels and the clinic findings was analyzed.Results Compared with the controls, all kinds of serum creatase levels in the patients elevated in different levels, and the differences were significant (all P
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Some Bemorheogical indexes of the middle-aged persom and the ages of "mental work pattem" health state were compared with that of the middle aged persen and the aged in general health in the paper, The authors found the values of the former were higher than that of the latter in varied degrees. Except the both sexes hematocrit and the male's erythrocyte sedimentation rate, the other inedxes of the both groups showed very significant differences. According to the cpidemiological data which showed the incidences of ischemic cardio-cerebrovascular diseases in the mental works were higher than that in the physical labourers, it is suggested that the differences of hemorheological characterislics in the both may be the one of the causes. The authors suggest that it should pay atterntion to health states of the middle aged person and the aged who had elementary normal conclusion in physical examination but they had abnormal high values of one or some hemorheological indexes.
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Objective To understand the diagnostic value of blink reflex (BR) in central neuropathy by observing the variations of blink reflex in diabetic patients. Methods Electrical pulse was used to stimulate the supraorbital nerve at the supraorbital notch. The responses of bilateral orbicular muscles of the eye were recorded, the variations of the latency and amplitude of R 1 and R 2 recorded on the side of stimulation and of R′ 2 recorded on the contralateral side were measured. Results There was significant prolongation in the latency and lowering of the amplitude of R 1, R 2 and R′ 2 in the diabetic patients compared with the control group. The abnormality rate of BR increased gradually with the prolongation of diabetic duration. Conclusion BR examination might provide an objective index for nervous damage in diabetic patients and it is helpful in early diagnosis of diabetic neuropathy.