Puerarin Up-regulates Methyl-CpG Binding Protein 2 Phosphorylation in Hippocampus of Vascular Dementia Rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD).</p><p><b>METHODS</b>Thirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively.</p><p><b>RESULTS</b>The morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (P<0.05), while the puerarin-treated group was obviously shorter than the dementia group (P<0.05). Cross-platform times of the dementia group were signifificantly decreased compared with the sham-operated group (P<0.05), while the puerarin-treated group was obviously increased compared with the dementia group (P<0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was signifificantly increased compared with the sham-operated group, and the puerarin-treated group was signifificantly increased compared with the dementia group (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with the sham-operated group, while it in the puerarin-treated group was signifificantly increased compared with the dementia group (P<0.05).</p><p><b>CONCLUSION</b>Puerarin could play a role in the protection of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron morphologies, and enhancing learning and memory ablities in a rat model of VD.</p>

Correlation between RoPE score and right-to-left shunt severity in patients with cryptogenic stroke / 西安交通大学学报(医学版)

Objective To compare the clinical features between cryptogenic stoke(CS)with and without right-to-left shunt(RLS)so as to determine whether shunt severity determined by control-enhanced transcranial Doppler(c-TCD)is correlated with the risk of paradoxical embolism(RoPE)score.Methods We made a retrospective analysis of clinical characteristics of 138 CS patients with and without RLS admitted to our department between January 2014 and November 2016.For patients documented by c-TCD,we evaluated whether there was a correlation between RLS severity and RoPE score. RLS was diagnosed by c-TCD and contrast-enhanced transthoracic echocardiography(c-TTE).We compared every modality for detecting RLS with and without Valsalva maneuver.For patients found with RLS in c-TCD and c-TTE,we judged whether there was an agreement in grading RLS between two modalities.Results For patients with CS,shunt severity by c-TCD was positively correlated with RoPE score(r= 0.26,P= 0.05).The clinical features were different between CS patients with RLS and without RLS.Compared with the positive results of c-TCD and c-TTE at rest,the positive rate was higher in Valsalva maneuver,respectively(P＜0.01).There was a moderate agreement between shunt grades identified by the two techniques(Kappa=0.428).Conclusion There is a positive correlation between RoPE score and RLS severity determined by c-TCD in CS patients.Valsalva maneuver can significantly increase the positive rate of RLS detected by c-TCD and c-TTE.

Effects of recombinant human erythropoietin on brain-derived neurotrophic factor expression in different brain regions of aging rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats.</p><p><b>METHODS</b>Forty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments.</p><p><b>RESULTS</b>Significant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region.</p><p><b>CONCLUSION</b>Treatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.</p>

Comparison of two contrast agents for diagnosis of patent foramen ovale by contrast transcranial Doppler / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare agitated saline solution (AS) and the mixture of AS with blood (ASb) as the contrast agents in contrast transcranial Doppler (c-TCD) in the diagnosis of patent foramen ovale (PFO).</p><p><b>METHODS</b>We recruited 248 consecutive patients for c-TCD examination between November 2015 and January 2016, and the sequence of the use of AS (9 mL saline solution mixed with 1 mL air) and ASb (9 mL saline solution and a drop of the patient's blood mixed with 1 mL air) was determined by coin-tossing method. Before the examination, the contrast agent was injected with or without Valsalva maneuvers (VM), and the number of microbubbles within 25 s after the contrast agent injection and the time of first appearance of microbubbles were recorded by observing the TCD spectrum. Each injection was repeated twice and the interval between tests was at least 5 min. We classified PFO according to the number of microbubbles into negative (no microbubble), grade I (1-10 microbubbles), grade II (>10 microbubbles but no curtain), and grade III (with curtain).</p><p><b>RESULTS</b>s The positivity rates in diagnosis with AS without VM, AS with VM, ASb without VM, and ASb with VM tests were 10.9%, 23.8%, 12.1% and 25.8%, respectively. AS with VM test had a higher positive rate than AS without VM test (23.8% vs 10.9%, P=0.001), and ASb with VM test had a higher positive rate than ASb without VM test (25.8% vs 12.1%, P=0.001). The positive rates were similar between ASb without VM and AS without VM test (12.1% vs 10.9%, P=0.250) and between ASb with VM test and AS with VM test (25.8% vs 23.8%, P=0.125).</p><p><b>CONCLUSION</b>VM can improve the positive rate of PFO diagnosis in c-TCD examination, and the positive rates are comparable between examinations using the contrast agents AS and ASb.</p>

Characteristic of microglial activation of hippocampus in experimental epileptic rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats.</p><p><b>METHODS</b>Morphological changes and proliferation of OX-42 positive cells were compared at different time points after status of epilepticus (SE) in lithium-pilocarpine induced epileptic rats.</p><p><b>RESULTS</b>OX-42 positive cells were activated after SE, which increased to a peak at 3-7 d and in a relatively stable state at 7-14 d; then gradually decreased after 14d and returned to slightly higher level than previously at 21 d.</p><p><b>CONCLUSION</b>Inflammatory injury, microglial activation and cell proliferation are closely related after seizures, microglial activation may be an important mechanism in the inflammatory injury of epilepsy.</p>

Effect of Helicobacter pylori infection on platelet activation and coagulation function in patients with acute cerebral infarction / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of Helicobacter pylori (Hp) on platelet activation and coagulation function in patients with acute cerebral infarction.</p><p><b>METHODS</b>Sixty-six patients with acute cerebral infarction and 50 health individuals were enrolled in the study. Hp antibody,expression of CD62p on platelets and clotting indexes were measured and compared between two groups.</p><p><b>RESULTS</b>The positive rate of Hp-IgG and Hp-CagA in cerebral infarction patients were higher than that in controls (P<0.05). The positive rate of CD62p in patients with positive Hp-IgG and Hp-CagA was significantly higher than that in negative patients and also controls (P<0.05). The APTT and TT were lower and FIB was higher in patients with positive Hp antibody than those in patients with negative Hp antibody (P<0.05),but there was no difference in PT,PTR and INR (P>0.05).</p><p><b>CONCLUSION</b>Hp infection can activate platelets and affect coagulation function,which may be involved in the development of cerebral infarction.</p>

Association of Helicobacter pylori infection and serum homocysteine level in patients with cerebral infarction / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the association of Helicobacter pylori infection and serum homocysteine(Hcy) levels with acute cerebral infarction.</p><p><b>METHODS</b>Serum Hp-IgG, Hp-CagA-IgG and Hcy were detected by biological micro-array analysis system in 85 patients with acute cerebral infarction and 40 healthy subjects (control group).</p><p><b>RESULTS</b>The positive rates of Hp-IgG and Hp-CagA-IgG significantly increased in cerebral infarction group compared with controls (P<0.05). There were significant differences in serum Hcy level between Hp-CagA-IgG positive and negative patients (P<0.05), but not between Hp-IgG positive and negative patients (P>0.05).</p><p><b>CONCLUSION</b>CagA-positive Hp infection may increase the risk of cerebral infarction, which might be associated with the increased serum homocysteine level.</p>

Expression of vascular endothelial growth factor and microvessel density in hippocampus of rats with aging / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in hippocampus of rats with aging.</p><p><b>METHODS</b>Paraffin sections of brain tissue of rats at the age of 3, 18, 24, 30 months were stained by immunohistochemistry, the expression of VEGF and MVD was quantitatively analyzed.</p><p><b>RESULTS</b>Innunohistochemical staining showed that the VEGF-positive cells were mainly pyramidal neuron in hippocampus; the intensity of VEGF-positivity in neuron cells was decreased with the aging (P<0.05). The MVD in hippocampus was also decreased with the aging of rats (P<0.05).</p><p><b>CONCLUSION</b>Increasing VEGF contents and improving blood circulation in brain tissue may prevent or treat vascular dementia and cerebrovascular diseases.</p>

Expression of glucose transporter-3 in the cerebral cortex of aging rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the changes in the expression of glucose transporter-3 (GLUT3) in the cerebral cortex of rats during aging and investigate the role of GLUT3 in the aging process of the nervous system.</p><p><b>METHODS</b>The cerebral tissues were collected from rats of 3, 18, 24, and 30 months old (10 in each age group), and the expression of GLUT3 in the cerebral cortex was detected by immunohistochemistry.</p><p><b>RESULTS</b>Under optical microscope, GLUT3-positive cells were found in every group. Within the age range of 3 to 8 months, GLUT3-positive cells increased significantly with age (P<0.01), but at 24-30 months of age, the number of GLUT3-positive cells reduced significant with age (P<0.01).</p><p><b>CONCLUSION</b>The expression changes of GLUT3 ir the cerebral cortex of rats during aging indicate that GLUT3 plays an important role in the maturation and aging of the nervous system.</p>

Expression of GLUT 3 in different brain regions of aged rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To examine the distribution of glucose transport 3 (GLUT 3) in different brain regions of aged rats and to investigate its role in ageing process of the nervous system.</p><p><b>METHODS</b>The GLUT 3 expression in different brain regions was examined with immunohistochemical method in rats aged 3, 18 and 30 months, respectively.</p><p><b>RESULTS</b>The number of GLUT 3-positive cells varied in the different brain regions in rats of all age groups (P<0.01); the CA1 region contained the greatest number of positive cells,and fewer in the motor cortex and cerebellum. The number of GLUT 3-positive cells was reduced in the brain of aged rats (P<0.01); and the neural cells in 4 different brain regions presented with large cell body and loose alignment.</p><p><b>CONCLUSION</b>The expression of GLUT 3 decreased in aged rats, which suggests that GLUT 3 may be involved in the ageing process of nervous system.</p>

Protective effects and mechanism of puerarin on learning-memory disorder after global cerebral ischemia-reperfusion injury in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action.</p><p><b>METHODS</b>The global cerebral ischemia-reperfusion injury model was established using the modifified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively.</p><p><b>RESULTS</b>(1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged signifificantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the puerarin group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the puerarin group was up-regulated at the respective time points after ischemia reperfusion (P<0.01), reaching the peak on day 1.</p><p><b>CONCLUSIONS</b>Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.</p>

Expression of Ref-1 in hippocampus CA1 area of rats with Alzheimer's disease / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the expression of Redox factor-1(Ref-1) in rats with Alzheimer's disease (AD).</p><p><b>METHODS</b>AD rat model was established by a single injection of beta-amyloid peptide (Abeta25-35) into the lateral cerebral ventricle of rats. Y-shape maze task was conducted to check the ethology. At 4th, 7th and 14th day after injection, Ref-1 expression in hippocampus CA1 area was detected by immunohistochemistry.</p><p><b>RESULT</b>The numbers of repeated learning and error and the total reaction time in AD group were significantly higher than those in control group at 7th and 14th day after injection of Abeta25-35 (P<0.05). At 4th day after injection of Abeta25-35, the Ref-1 expression was increased with time prolongation in AD group(P<0.01).</p><p><b>CONCLUSION</b>Injection of Abeta25-35 in lateral cerebral ventricle can decrease the learning and memory abilities of rats, and results also indicate that Ref-1 expression in hippocampus may be involved in the development of AD.</p>

Expression of p38MAPK in the hippocampal CA1 region of rats with Abeta25-35-induced Alzheimer disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of p38MAPK expression in a rat model of Alzheimer disease (AD).</p><p><b>METHODS</b>Seventy-two adult SD rats were randomized equally into 4 groups, and a single-dose injection of Abeta25-35 (dementia group), normal saline (saline group), SB203580 (inhibitor group), or DMSO (inhibitor control group) was administered into the lateral cerebral ventricle. Y-maze tast was performed to evaluate the behavioral changes of the rats after the injections, and on days 4, 7 and 14 after the injection, p38MAPK expression in the hippocampal CA1 area was measured by means of immunohistochemistry.</p><p><b>RESULTS</b>On days 7 and 14 following Abeta25-35 injection, the training times, error number and total reaction time were significantly higher in dementia group than in saline group (P<0.05), but all these indices were significantly lowered in the inhibitor group as compared with the dementia group (P<0.05). Immunohistochemistry revealed obvious p38 expression in the dementia group 4 days after Abeta25-35 injection, which increased significantly with the passage of time (P<0.01). The gray scale in the inhibitor group was significantly higher than that in the dementia group (P<0.01).</p><p><b>CONCLUSION</b>p38MAPK activation in the hippocampal CA1 area is an event that persists during the entire course of Abeta25-35-induced AD in rats, and the inhibitor SB203580 prevents p38MAPK expression and improves the learning and memory abilities of the rats.</p>

Expression of hypoxia inducible factor-1alpha in different brain regions in aged rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the distribution of hypoxia inducible factor-1alpha (HIF-1alpha) in different brain regions in aged rats and investigate the role of HIF-1alpha in the aging process of the nervous system.</p><p><b>METHODS</b>The Nissl bodies and HIF-1alpha expression in different brain regions were observed in rats aged 3 and 30 months using Nissl staining and immunohistochemical method, respectively.</p><p><b>RESULTS</b>In the 30-month-old rats, the neural cells in 4 different brain regions presented with large cell body and loose alignment, containing reduced Nissl bodies in the cytoplasm. Compared with the 3-month-old rats, the aged rats showed greater number of HIF-1alpha-positive cells in the brain (P < 0.01), and the number varied significantly between the different brain regions (P < 0.01). The CA3 region contained the greatest number of positive cells, which were fewer in the motor cortex and cerebellum.</p><p><b>CONCLUSION</b>The capacity for protein synthesis in the neural cells is weakened but the expression of HIF-1alpha increased in aged rats, suggesting the important role that HIF-1alpha may play in the aging process of the nervous system, especially in hypomnesis.</p>