Inhibition of SNK-SPAR signaling pathway promotes the restoration of motor function in a rat model of ischemic stroke.

This study aimed to investigate the effects of SPAR signaling pathway on the restoration of motor function in ischemic stroke (IS). Sprague-Dawley male rats were separated into the control and sham groups, as well as the group for middle cerebral artery occlusion (MCAO) model establishment. Successfully established rat ischemic models were randomly divided into model, SNKMCAO-del and pcDNA3.1-SNK groups. The evaluation of motor function among the rats in each group was assessed using a balance beam, a screen test and the Garcia scoring method. CatWalk gait analysis was employed to evaluate the effect of the SNK signaling pathway on rat motor function. Triphenyltetrazolium chloride (TTC) and TUNEL staining were techniques were utilized for cerebral infarction (CI) area as well for hippocampal neuron apoptosis. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting methods were performed to detect mRNA and protein expressions of SNK and SPAR. When compared with the model group, the SNKMCAO-del group displayed decreased motor function score and CI area, while contrasting results were observed in the pcDNA3.1-SNK group. According to the results obtained from the CatWalk gait analysis, the SNKMCAO-del group showed a clear improvement compared to the model group whereas the pcDNA3.1-SNK group exhibited poorer results than the model group in the objective parameters of the study, such as movement, speed, running duration, print area, maximal contact area, maximal, mean intensity, and stride length. These findings suggested that SNK gene silencing promotes motor function by inhibiting the SNK-SPAR signaling pathway in rats with ischemic stroke.

Diagnostic accuracy of intracellular mycobacterium tuberculosis detection for tuberculous meningitis.

RATIONALE: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. OBJECTIVES: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. METHODS: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis. MEASUREMENTS AND MAIN RESULTS: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively. CONCLUSIONS: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.

[The effect of edaravone on MAPKs signal pathway associated with Abeta(25-35) treatment in PC12 cells].

OBJECTIVE: To explore whether edaravone protects cells damage via mitogen-activated protein kinases (MAPKs) signal pathway, and which procedure of p38 be affected so as to add theories for AD pathogenesis and treatments. METHODS: According to different drugs treated, PC12 cells in vitro were divided into four groups. Negative control group: cells were treated with media alone. AD model group: cells were treated with 30 pmol/L Abeta(25-35). Inhibitor control group: cells were treated with 10 micromol/L SB203580 Cp38 mitogen-activated protein kinase (p38) inhibitor], 10 micromol/L SP600125 [c-Jun NH2 terminal kinase (JNK) inhibitor], or 10 micromol/L PD98059 extracelular signal regulated kinase (ERK) inhibitor]. Low-dose, middle-dose and high-dose edaravone group: cells plated for 24 hours treated with 30 micromol/L Abeta(25-35) and co-treated with 20, 40, 80 micromol/L edaravone 3 hours, respectively. The morphology of the treated cells were observed, the p-p38, p-JNK and p-ERK proteins in each group were tested by the Western blot. The p38 mRNA were tested in each group above (only add SB203580 10 micromol/L in third group) by the real time PCR. RESULTS: (1) The p-p38 protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-p38 protein in the inhibitor group and edaravone groups was decreased significantly (P<0.05) when compared with that in model control group. The p-p38 proteins were significantly increased in the three edaravone groups compared with that in inhibiter control group (P<0.05). The p-p38 protein in middle-dose edaravone group was decreased compared with that in low-dose edaravone group (P<0.05). There was no relationship in dose-dependent manner about edaravone. Compared with three edaravone groups, the p-p38 protein was lower than it in high-dose edaravone & inhibiter group (P<0.05). (2) The p-JNK protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-JNK protein in the inhibitor group was decreased compared with that in model control group (P<0.05). (3) No significantly difference of p-ERK protein concentration was observed in other groups when compared with that in negative control group (P>0.05 each). (4) Compared with negative control group, the p38 mRNA in model control group was significantly increased, and it was significantly decreased in inhibitor control group (P<0.05 each). In 40 micromol/L and 80 micromol/L edaravone groups, the p38 mRNA was significantly decreased compared with that in model control group, and it still was decreased compared with that in inhibitor control group (P<0.05). The p38 mRNA in 40 micromol/L edaravone group was the lowest among three edaravone groups, and it was obviously different from that in 20 micromol/L and 80 micromol/L edaravone groups (P<0.05). CONCLUSION: Abeta(25-35) could increase the p-p38 and p-JNK protein expression in cultured PC12 cells, but there was no obviously expression of p-ERK protein. These indicated that Abeta(25-35) might activate MAPKs signal pathway, especially p38 and JNK, and lead to PC12 cell damage. Edaravone could decrease p38 mRNA induced-Abeta(25-35), which indicated edaravone could protect PC12 cell damage via blocking p38 signal pathway in mRNA stage and protein stage simultaneously. Hence, it is promising that edaravone would be a new medicine for AD.

[Association of Helicobacter pylori infection and serum homocysteine level in patients with cerebral infarction].

OBJECTIVE: To investigate the association of Helicobacter pylori infection and serum homocysteine(Hcy) levels with acute cerebral infarction. METHODS: 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). RESULTS: 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). CONCLUSION: CagA-positive Hp infection may increase the risk of cerebral infarction, which might be associated with the increased serum homocysteine level.

[Characteristic of microglial activation of hippocampus in experimental epileptic rats].

OBJECTIVE: To investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Effect of Helicobacter pylori infection on platelet activation and coagulation function in patients with acute cerebral infarction].

OBJECTIVE: To investigate the effect of Helicobacter pylori (Hp) on platelet activation and coagulation function in patients with acute cerebral infarction. METHODS: 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. RESULTS: 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). CONCLUSION: Hp infection can activate platelets and affect coagulation function,which may be involved in the development of cerebral infarction.

[The anti-aging effect of EPO and the preliminary probe into its mechanisms].

OBJECTIVE: To study whether erythropoietin ( EPO) has the anti-aging effect and the mechanisms of how it effects. METHODS: 5% D-galactose hypodermic injection for 6 weeks to establish the aging model. Divided rats into 5 groups randomly: the normal control (group A), the aging model (group B), the low dosage (1 000 U/ (kg x d)) of recombinant human erythropoietin (rhEPO) intervene (group C), the middle dosage (3 000 U/(kg x d)) of rhEPO intervene (group D) and the high dosage (5 000 U/(kg x d)) of rhEPO intervene (group E), 10 rats in each group. Morris water maze was used to comparing the behavioral indexes. After decapitating the rats, the malonaldehyde (MDA), Na(+)-K+ ATPase, total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) of brain tissue were tested. One rat from each group was selected randomly to observe the hippocampal ultramicrostructure. RESULTS: (1) Compared with group A, the learning and memory ability of group B reduced, the level of MDA, the Na(+)-K+ ATPase, T-AOC and the SOD activities of brain tissue decreased (P < 0.05), besides, a series of aging changes were observed in the hippocampal ultramicro-structure in group B. (2) Compared with group B, an improved learning and memory ability of group D, a reduced MDA content and an increased activity of Na(+)-K+ ATPase, T-AOC and the SOD activities of brain tissue in group D were also observed with a improved hippocampal ultramicro-structure. (3) The low dosage of rhEPO intervention could against the decrease of the activities of brain Na(+)-K+ ATPase, SOD of aging rat (P < 0.05), but had no significant effects on the rest of the indicators. The high dosage of rhEPO intervention had no significant improvements on various indicators of aging rats in high dosage of rhEPO intervention group was noticed (P > 0.05). CONCLUSION: The middle dosage of EPO has the anti-aging effect, and its mechanisms may be related to enhancing the antioxidant enzymes activity and increasing the antioxidant capacity.

[Effect of puerarin on the expression of NMDA receptor in the hippocampus CA1 region after focal cerebral ischemia in rats].

OBJECTIVE: To study the antagonistic action of Puerarin against the excitatory amino acid toxicity, and to further explore its brain protection mechanisms. METHODS: Focal cerebral ischemia model was set up with middle cerebral artery occlusion by intraluminal block in this study. After cerebral ischemia, Puerarin was administered at different time point. The volume of cerebral ischemia was assessed by TTC stain. NR1 positive neurons in hippocampus CA1 region was determined by immunohistochemistry SABC method. RESULTS: The cerebral ischemia volumes were smaller in 2 h and 12 h model treatment groups (P < 0.05) than those in model control groups, but no significant differences were observed in 24 h model treatment group. Compared with sham-operation group, the NR1-positive cells in hippocampal CA1 region were increased obviously (P < 0.05) in both model control and model treatment groups. Compared with model control groups, the NR1-positive cells in hippocampal CA1 were decreased obviously (P < 0.05) in 2 h and 12 h treatment groups. CONCLUSION: The treatment of Puerarin within 12 h after ischemia can cut down the expression of NMDA receptor. This indicates that the puerarin treatment in earlier period after ischemia can indirectly rivalry toxic effect of excitatory amino acids, relieve neural injury.

[Expression of vascular endothelial growth factor and microvessel density in hippocampus of rats with aging].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in hippocampus of rats with aging. METHODS: 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. RESULTS: 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). CONCLUSION: Increasing VEGF contents and improving blood circulation in brain tissue may prevent or treat vascular dementia and cerebrovascular diseases.

[Expression of GLUT 3 in different brain regions of aged rats].

OBJECTIVE: 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. METHODS: The GLUT 3 expression in different brain regions was examined with immunohistochemical method in rats aged 3, 18 and 30 months, respectively. RESULTS: 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. CONCLUSION: The expression of GLUT 3 decreased in aged rats, which suggests that GLUT 3 may be involved in the ageing process of nervous system.

[Hypoxia inducible factor-1alpha expression trends in hippocampus of rat of different ages].

OBJECTIVE: To reveal the expression trends of HIF-1alpha in hippocampus of different age rats, investigate the role of HIF-1alpha in the aging process of nervous system. METHODS: The cerebral tissues was collectd from rats of different age, including 3, 18, 24, 36 months old. There were 6 rats in each age group. The expressions of nissl body and HIF-1alpha in different part of hippocampus were observed by nissl staining and immunohistochemical technique. RESULTS: (1) With the increase of rat age, nerve cells appeared to be bigger and to arrange sparsely, while the nissl body decreased; (2) The positive HIF-1alpha staining cells in CA1, CA3 region of hippocampus increased along with the increase of rat age. The difference between any two age groups showed statistical significance (P < 0.05). CONCLUSION: The function of protein synthesis weakened in nerve cells but the expression of HIF-1alpha increased with the age increasing, which may play an important role in aging of nervous system.

[Expression of p38MAPK in the olfactory bulb of rats with Alzheimer's disease].

OBJECTIVE: To identify the changes of expression of p38MAPK in the olfactory bulb (OB) of rats with Alzheimer's Disease (AD) and to explore the functional mechanism of p38MAPK in the pathological changes of AD. METHODS: AD animal model was established by injecting amyloid-beta peptide 25-35 into the lateral cerebral ventricle of rats. The learning and memory abilities of rats were measured by Y-maze experiment. The expressions of p38MAPK in the OBs of rats in the AD group, saline control group, p38MAPK inhibitor group and inhibitor control (con-inhibitor) group were examined by immunohistochemistry. RESULTS: (1) The capabilities of learning and memory of the rats were impaired significantly at day 7 and day 14 after the induction of AD. Significant learning and memory differences were found (P < 0.05) between the AD group and the other groups. (2) The expression of p38MAPK in the OBs of rats was found at day 4 after the induction of AD. The expression increased with time. The AD rats had more positive p38MAPK cells than those in the saline controls (P < 0.05). The expression of phospho-p38MAPK in the rats with AD increased significantly (P < 0.01) compared with those in the saline group. The AD rats treated with p38MAPK inhibitor had less expression of phospho-p38MAPK than those in the AD group and the inhibitor control (P < 0.01). CONCLUSIONS; Abeta25-35 can activate p38MAPK signal transduction pathway. p38MAPK may play a role in the formation of dysosmia in AD. SB203580, a p38MAPK inhibitor, can reduce the neurotoxicity evoked by p38MAPK.

[Expression of Ref-1 in hippocampus CA1 area of rats with Alzheimer's disease].

OBJECTIVE: To investigate the expression of Redox factor-1(Ref-1) in rats with Alzheimer's disease (AD). METHODS: 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. RESULT: 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). CONCLUSION: 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.

Puerarin Up-regulates Methyl-CpG Binding Protein 2 Phosphorylation in Hippocampus of Vascular Dementia Rats.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Different Valsalva Manoeuvre Procedures for the Diagnosis of Right-to-Left Shunt by Contrast-Transcranial Doppler.

The main purpose of this study was to compare two contrast agent injection times during the Valsalva manoeuvre (VM) for the diagnosis of right-to-left shunt using contrast-transcranial Doppler (c-TCD). In total, 992 consecutive patients underwent testing. All patients underwent step 1, and then a coin toss was used to determine the order of steps 2 and 3. The following testing steps were repeated twice: (1) a contrast agent (CA) was infused at rest (CA at rest testing); (2) the VM was initiated immediately after CA injection and released 10 s after CA injection (CA pre-VM testing); and (3) a CA was injected 5 s after initiating the VM, which was released 5 s after CA injection (CA mid-VM testing). For the CA at rest, pre-VM and mid-VM groups, significant differences were observed in the positive right-to-left shunt diagnosis rates (11.49% vs. 23.08% vs. 26.11%, respectively, with an inter-group significance of p < 0.05) and grade classifications (p < 0.05). Although the times to first microbubble appearance were similar between the CA at rest and the CA pre-VM groups (8.96 ± 3.40 s vs. 8.42 ± 3.72 s, p > 0.05), it was shorter (6.4 ± 2.75 s, p < 0.05) for the CA mid-VM group than for the other two groups. For the c-TCD testing, the CA mid-VM group yielded different results for diagnosing right-to-left shunts relative to the CA pre-VM group.

[A study on expression of HIF-1alpha and EPO in the hippocampus of rats with vascular dementia].

OBJECTIVE: To observe the expression rule of hypoxia inducible factor-1 (HIF-1alpha) and erythropoietion (EPO) in the formation of vascular dementia (VD) and investigate the possible pathogenesis of VD. METHODS: Rats of experimental group were treated with a permanent bilateral common carotid arteries (CCA) occlusion (2-VO) for establishing vascular dementia model. Rats were evaluated on learning-memory ability by Y-type water maze test. The dynamic expression of HIF-1alpha and EPO in hippocampal CA1 region were measured by immunohistochemical assay method. RESULTS: (1) The learning-memory ability of rats in VD groups was progressively decreased as the ischemic duration prolonged (P < 0.05); (2) In VD group, the expression of HIF-1alpha and EPO in hippocampal CA1 region were most obvious at 1 w, and then declined progressively but still above the normal level (P < 0.01); (3) In VD group, the expression of HIF-1alpha and EPO at each ischemic point and their corresponding learning-memory ability were in significant correlation at the 0.01 level. CONCLUSION: Both HIF-1alpha and EPO contribute to the formation of VD, and HIF-1/EPO anoxic signal transduction may play a protecting role in this process.

[Comparison of two contrast agents for diagnosis of patent foramen ovale by contrast transcranial Doppler].

OBJECTIVE: 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). METHODS: 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). RESULTS: 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). CONCLUSION: 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.

[Effects of recombinant human erythropoietin on brain-derived neurotrophic factor expression in different brain regions of aging rats].

OBJECTIVE: To explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Immature dendritic cell exosomes suppress experimental autoimmune myasthenia gravis.

Immature dendritic cell-derived exosomes (iMDEX) display a certain degree of immunosuppressive activity in autoimmune diseases. However, the role of iMDEX in experimental autoimmune myasthenia gravis (EAMG) is still unclear. Therefore, we tested the effects of mouse bone marrow (BM)-derived iMDEX on tolerance induction in a mouse model of EAMG. In this study, we found that the CELLine culture system produced more exosomes, the morphology and phenotype of these exosomes were found to be identical when compared with traditional cell culture. And, iMDEX(1000) ameliorated the progression of EAMG by reducing AChR-reactive lymphocyte proliferation, AChR antibody levels and pro-inflammatory cytokine levels.