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Objective: To investigate the effect and mechanism of Xiaoyaosan on lipopolysaccharide(LPS)-induced nerve injury. Method: The 56 rats were randomly divided into control group, sham group, model group, amitriptyline group (10 mg·kg-1), fluoxetine group (10 mg·kg-1), Xiaoyaosan group high and low-dose (30,15 g·kg-1).The nerve injury model rat were established by LPS injection into lateral ventride, rats were administrated for 14 days by gavage. The levels of brain-derived neurotrophic factor (BDNF) and β-nerve growth factor (β-NGF) in serum were detected by enzyme linked immunosorbent assay(ELISA), and the expressions of BDNF, nerve growth factor (NGF), tropomyosin receptor kinase B (TrkB), tropomyosin receptor kinase A (TrkA), cAMP response element-binding protein (CREB) mRNA in hippocampus and cortex were detected by Real-time PCR.Protoin expression of BDNF, TrkB, CREB, p-CREB, postsynaptic density protein 95 (PSD95), synaptophysin (SYP) in hippocampus and cortex were detected by Western blot. Result: Compared with control group, LPS decreased the level of BDNF and β-NGF in serum(PPPβ-NGF in serum in Xiaoyaosan high and low-dose group were increased significantly (PPPPConclusion: Xiaoyaosan has a certain antagonistic effect on LPS inducednerve injury, which suggests that the effect is related to activate BDNF/NGF-TrkB/TrkA-CREB pathway and upregulated the expression of synaptic protein.
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@#Retinal diseases and optic nerve injury blocked visual signal transduction from retinal neurons to visual cortex, which would cause significant influence on patients' visual function and life quality. In clinic, glaucoma, traumatic optic neuropathy, and retinitis pigmentosa and so on are accompanied with degeneration of retinal neurons or optic nerve. However, efficient neuro-protective treatment is limited. Currently, studies suggested neuro-protective and regenerative effect of electrical stimulation treatment on retinal neurons and optic nerves. In this study, we reviewed the application of electrical stimulation in ophthalmology and summarized the possible mechanism, aiming to promote the development of electrical stimulation in the study and treatment of eye diseases.
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Objective To investigate the effect of microRNA-22 (miRNA-22) on the expression of P2X7 receptor and inflammatory factors in hippocampus of rats with epilepsy. Methods Healthy SD male rats were intraperitoneal injected with lithium chloride and pilocarpine to induce epilepsy. Three days later, 45 epileptic rats were randomly divided into three groups: epilepsy group( EP group), miRNA-22 agomir group (EF+agomir group) and miRNA-22 agomir control group ( EF+agomir control group). Another 15 healthy rats were selected as control group(N group). The expression of P2X7 protein was detected by West- ern blot and the levels of miRNA-22, P2X7 mRNA, NF-κB mRNA ,IL-1β mRNA were detected by qRT-PCR. Nissl staining was used to observe the damage of Nissl bodies. Results Western blot result showed that compared with the N group(0. 91±0. 10), the level of P2X7 protein in EP group (1. 17±0. 052) in-creased, and the difference was statistically significant (t=-4. 11,P=0. 02). Compared with the EP+ag-omir control group(0. 94± 0. 14),the expression of P2X7 protein in EP+agomir group (0. 66± 0. 06) de-creased and the difference was significant (t=-3. 10,P=0. 04). And the qRT-PCR results showed that compared with N group, the levels of P2X7mRNA (9. 08±0. 94), NF-κB mRNA (20. 10±2. 15) and IL-1β mRNA (50. 64±5. 42) in EP group increased(t=-14. 96,P<0. 05; t=-15. 38,P<0. 05; t=-15. 87,P<0. 05). The expression of P2X7mRNA (1. 31 ± 0. 64), NF-κB mRNA ( 2. 28 ± 1. 10) and IL-1β mRNA (2. 12±1. 20) in EF+agomir group decreased compared with EP group((9. 08± 0. 94),( 20. 10± 2. 15), (50. 64±5. 42)) and EF+agomir control group((7. 03 ±1. 90),(18. 72±1. 76),(47. 39±6. 16)), and the differences were statistically significant(F=29. 77, P<0. 01;F=98. 99, P<0. 05;F=96. 29, P<0. 01). Nissl staining results showed that a large number of morphologically abnormal and disintegrated Nissl bodies could be observed in the hippocampal CA1 and CA3 regions of EP group,which showed a smaller size,irreg-ular morphology,chromatin pyknosis,boundary blur between nucleus and cytoplasm. Compared with the nor-mal group, the difference was significant (P<0. 05). While in miRNA-22 agomir group, the disintegration of Nissl bodies was improved and the number of Nissl bodies increased. Conclusion Intraventricular injec-tion of miRNA-22 agomir can down-regulate the expression of P2X7 receptor and related inflammatory factors in hippocampus of epileptic rats, thus inhibiting seizures.
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Objective To observe the neuro-protective effect of Levocarnitine on severe hand,foot and mouth disease (HFMD) after enterovirus 71 (EV71) infection,to preliminarily explore the possible mechanism preliminarily.Methods One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Chihlren's Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases,including 32 males and 34 females,median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levocarnitine group (66 cases,including 36 males and 30 females,median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females,median age of 2 years and 6 months) who were examined at the Children's Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100,NSE,soluble apoptosis-related factors (sFas),soluble apoptosis-related factor l igands (sFasL),malondialdehyde (MDA),superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum,efficacy-related indicators such as duration of fever,white blood cell count on the 3rd day of treatment,time to remission of nervous system symptoms,time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas,sFasL,MDA,SOD and S100,NSEwas performed Results (1) The levels of S100 [(0.38:±:0.16) μg/Lvs.(0.06:±:0.23) μg/L],NSE [(43.70±8.80) μg/Lvs.10.10±3.60) μg/L],sFas [(6.61 ±1.86) μg/Lvs.(3.88±1.22) μg/L],sFasL [(101.40±20.7) μg/Lvs.(54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/Lvs.(4.08±1.45) nmol/L]in serum of HFMD group were significantly higher than those of the healthy control group (t =-12.245,-22.895,-8.273,-12.803,-17.960,all P ＜0.05),while the SOD level [(57.10 ± 10.40) kU/L vs.(70.3 ±14.4) kU/L] was significantly lower (t =5.457,P ＜ 0.05).(2) With the extension of treatment time for HFMD children in the two groups,S100 and NSE in cerebrospinal fluid,S100,NSE,sFas,sFasL and MDA in serum decreased,while SOD level increased.On the 3rd and 7th day after treatment,S100 (t3 =3.491,t7 =14.434),NSE (t3 =2.920,t7 =23.490) in cerebrospinal fluid,S100 (t3 =5.277,t7 =3.614),NSE (t3 =4.652,t7 =10.525),sFas (t3 =6.399,t7 =7.514),sFasL (t3 =11.155,t7 =8.804) and MDA (t3 =6.348,t7 =7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P ＜ O.05),while SOD (t3 =3.162,t7 =-3.529) was significantly higher than that of routine group (P ＜0.05).(3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23 ± 0.65) d vs.(1.84 ± 0.47) d],and WBC on the 3rd day after treatment [(9.14 ± 2.93) × 109/L vs.(7.12 ± 2.58) × 109/L] and the progression time of the disease [(29.74 ± 7.85) h vs.(17.36 ± 8.73) h] were significantly better than the those in the routine group (t =-6.178,4.204,8.567,all P ＜ 0.05).The critical conversion rates of Levocarnitine group and the routine group were 7.58％ and 18.18％,respectively,and the difference in critical conversion rate was not statistically significant (x2 =2.316,P ＞0.05).(4)There was a positive correlation between S100 and sFas,sFasL,MDA in children with HFMD (r =0.373,0.735,0.334,P ＜ 0.05).NSE was positively correlated with sFas and sFasL (r =0.479,0.601,all P ＜0.05),while SOD and S100 were negatively correlated with NSE (r =-0.425,-0.460,all P ＜ 0.05).Conclusions Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71,which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.
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Objective@#To observe the neuro-protective effect of Levocarnitine on severe hand, foot and mouth disease (HFMD) after enterovirus 71(EV71) infection, to preliminarily explore the possible mechanism preliminarily.@*Methods@#One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Children′s Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases, including 32 males and 34 females, median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levo-carnitine group (66 cases, including 36 males and 30 females, median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females, median age of 2 years and 6 months) who were examined at the Children′s Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100, NSE, soluble apoptosis-related factors (sFas), soluble apoptosis-related factor ligands (sFasL), malondialdehyde (MDA), superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum, efficacy-related indicators such as duration of fever, white blood cell count on the 3rd day of treatment, time to remission of nervous system symptoms, time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas, sFasL, MDA, SOD and S100, NSE was performed@*Results@#(1) The levels of S100 [(0.38±0.16) μg/L vs. (0.06±0.23) μg/L], NSE [(43.70±8.80) μg/L vs. 10.10±3.60) μg/L], sFas [(6.61±1.86) μg/L vs. (3.88±1.22) μg/L], sFasL[(101.40±20.7) μg/L vs. (54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/L vs. (4.08±1.45) nmol/L] in serum of HFMD group were significantly higher than those of the healthy control group (t=-12.245, -22.895, -8.273, -12.803, -17.960, all P<0.05), while the SOD level [(57.10±10.40) kU/L vs. (70.3±14.4) kU/L] was significantly lower (t=5.457, P<0.05). (2) With the extension of treatment time for HFMD children in the two groups, S100 and NSE in cerebrospinal fluid, S100, NSE, sFas, sFasL and MDA in serum decreased, while SOD level increased.On the 3rd and 7th day after treatment, S100 (t3=3.491, t7=14.434), NSE (t3=2.920, t7=23.490) in cerebrospinal fluid, S100 (t3=5.277, t7=3.614), NSE (t3=4.652, t7=10.525), sFas (t3=6.399, t7=7.514), sFasL (t3=11.155, t7=8.804) and MDA (t3=6.348, t7=7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P<0.05), while SOD (t3=3.162, t7=-3.529) was significantly higher than that of routine group (P<0.05). (3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23±0.65) d vs. (1.84±0.47) d], and WBC on the 3rd day after treatment [(9.14±2.93)×109/L vs. (7.12±2.58)×109/L] and the progression time of the disease [(29.74±7.85) h vs. (17.36±8.73) h] were significantly better than the those in the routine group (t=-6.178, 4.204, 8.567, all P<0.05). The critical conversion rates of Levocarnitine group and the routine group were 7.58% and 18.18%, respectively, and the difference in critical conversion rate was not statistically significant (χ2=2.316, P>0.05). (4)There was a positive correlation between S100 and sFas, sFasL, MDA in children with HFMD (r=0.373, 0.735, 0.334, P<0.05). NSE was positively correlated with sFas and sFasL (r=0.479, 0.601, all P<0.05), while SOD and S100 were negatively correlated with NSE (r=-0.425, -0.460, all P<0.05).@*Conclusions@#Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71, which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.
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RESUMEN El estudio focalizado en dilucidar el rol neuroprotector del ARA y del DHA a lo largo del ciclo vital ha cobrado cada vez más interés puesto que se continúan descubriendo mecanismos mediante los cuales estos ácidos grasos poliinsaturados de cadena larga (AGPICL) modulan el metabolismo. Tanto el ARA como el DHA se encuentran depositados en los lípidos de las membranas de las células que forman la materia gris y representan aproximadamente el 25% del contenido total de ácidos grasos cerebrales. El ARA y el DHA tienen efectos sobre el crecimiento y la diferenciación neuronal a través de la modulación de las propiedades físicas de la membrana, de la transducción de señales asociada a proteínas G y la modulación de la expresión génica, adquiriendo un rol relevante en la neuro-génesis y el desarrollo cerebral. Además, se les atribuye un rol neuroprotector en patologías neurodegenerativas como la enfermedad de Alzheimer y la enfermedad de Parkinson, pudiendo disminuir la disfunción mitocondrial, la neuro-inflamación y el estrés oxidativo, expresiones características de estas patologías. La presente revisión analiza y discute acerca del rol del ARA y del DHA en la neuro-protección y en la neurodegeneración a través de una visión integradora.
ABSTRACT The study focused on elucidating the neuro-protective effects of ARA and DHA throughout the life cycle has become of increasingly interest since the continue discovering of mechanisms by which these long-chain polyunsaturated fatty acids (LCPUFA) modulate the metabolism. Both ARA and DHA are deposited into the membrane lipids of the cells that form the gray matter of the brain and represent approximately 25% of the total content of cerebral fatty acids. ARA and DHA have effects on the growth and neuronal differentiation through the modulation of the physical properties of the membrane, the signal transduction associated to G proteins and by the modulation of gene expression, acquiring a relevant role in neurogenesis and brain development. In addition, it is attributed to these fatty acids a neuro-protective role in neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease by decreasing the mitochondrial dysfunction, neuroinflammation and oxidative stress, characteristic of these pathologies. This review analyzes and discusses the role of ARA and DHA in neuro-protection and neuro-degeneration through an integrative vision.
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Humans , Parkinson Disease , Docosahexaenoic Acids , Arachidonic Acid , Alzheimer Disease , Neurons , Neurodegenerative DiseasesABSTRACT
Aim To investigate the effects of salidroside on NeuN and Egrs in the ischemic side of middle cerebral artery occlusion (MCAO) rats by inhibiting complement C3.Methods The rats were subjected to MCAO with suture-occluded method,and the neurologic injury was evaluated.The rats underwent l h ischemia/reperfusion with 1 d and 2d salidroside treatment,and the expressions of NeuN,Egr4,C3 and C1 were tested.Male Sprague Dawley rats were separately injected ventricle C3aR inhibitor and artificial cerebrospinal fluid with the help of ventricle stereotaxic apparatus.Thirty min later,the models of MCAO were finished with 1h reperfusion,drug administration and intracerebroventricular injection for 2d.The expressions of NeuN,Egr4,C3 were detected.Results Compared with models of MCAO,the expression of C3 in MCAO rats treated with salidroside 1 d and 2d decreased significantly,and the expression of NeuN increased markedly.Salidroside had no apparent effect on Egr4 and C1 of administration of 1d,but it could significantly enhance the expression of Egr4 after 2d,and reduce the expression of C1 significantly after 2d.The rats administrated with C3aR inhibitor into cerebral ventricle continueously showed the same result in accordance with the treatment of salidroside.And the treatment of salidroside and C3aR inhibitor did not show remarkable additive effects.Conclusion The neuroprotective effect of salidroside on acute cerebral ischemia/reperfusion injury may be related to the inhibition of the activation of the classical pathway of complement,the regulation of Egrs and the reduction of apoptosis.
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Objective To investigate the effects and mechanisms of valproic acid on brain edema,neurobehavioral outcome and inflammatory response after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Fifty-four SD male rats,weighting 220-250 g,were randomly divided into 3 groups (n =18):sham operation group (group sham),traumatic brain injury group (group TBI) and valproic acid treatment group (group TBI + VPA).Experimental rats were treated with valproic acid (300 mg/kg,twice daily) by intraperitoneal injection.Rat behavioral outcomes were measured by modified neurologic severity score (mNSS) tests at day 1,3,and 7 after TBI.Brain water content was measured with wet-dry weight method.The blood cells infiltration into cerebral cortex were tested with immunohistochemistry staining against ED-1 for macrophage.Inflammatory cytokines (INF-γ,tumor necrosis factor-α,interleukin-6) were measured by Western blotting.The statistical analysis were performed by ANOVA and chi-square tests using the statistical software program SPSS 13.0.Results Compared with the Sham group,the levels of brain edema,mNSS and macrophage cell infiltration were significantly increased after TBI (all P =0.00).The expressions of inflammatory cytokines were also increased significantly (all P =0.00).Compared with the TBI group,TBI + VAP group had significantly lower brain water content[3day:(80.12 ±0.59)％ vs.(82.14 ±0.67)％,P=0.04;7day:(74.74 ±0.72)％ vs.(77.93 ±0.48)％,P=0.01],and mNSS scores [3 day:(10.53 ±0.32) vs.(11.74 ±0.48),P =0.02;7 day:(7.97 ± 0.32) vs.(10.73 ± 0.42),P =0.01].VPA suppressed macrophage cell infiltration into cerebral cortex [(36.44 ± 0.72) ％ vs.(25.93 ± 0.48) ％ P =0.00].Meanwhile,VPA inhibited the expressions of inflammatory cytokines (INF-γ,TNF-α,IL-6) (P ＜ 0.05).Conclusions Treatment with VPA markedly reduced brain edema and improved neurological outcomes after TBI,possibly mediated by inhibited TBI-induced cerebral inflammatory responses and macrophage cell infiltrating into cerebral cortex.
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OBJECTIVE: To determine the neuro-protective effects of albiflorin against MPP+-induced PC12 cells death and related molecular mechanisms. METHODS: PC12 cells were treated with 4 mmol·L-1 MPP+ to establish apoptotic cell models. MTT method, DCFH-DA staining, JC-1 staining and Western Blot were used to determine the changes of cell viability, intracellular ROS concentration, mitochondrial membrane potential and the expression of Bel-2 and Bcl-X1, and the phosphoration of Akt/GSK3β in PC12 cells. RESULTS: Albiflorin showed significantly neuro-protective effects against MPP+-induced cell damage. Results showed that albiflorin enhanced the cell viability, reduced intracellular ROS level and caspase 3 activation, restored the mitochondrial membrane potential, increased the expression of Bcl-2 and Bcl-X1, and enhanced the phosphoration of Akt/GSK3β. CONCLUSION: Albiflorin shows neuro-protective effects against MPP+-induced PC12 cells damage via mitochondrial-dependent pathway and Akt/GSK3β signaling.
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@#H2S has a role of protecting neurons from ischemia-reperfusion injury and significantly reducing the cerebral infarction area, but high concentration of H2S can induce neurotoxicity. Memantine, a N-methyl-D-aspartic acid(NMDA)receptor antagonist, could reduce the neurotoxicity of H2S at high concentration. Nine novel structures(compounds I1-I9)were designed by coupling(4-hydroxy phenyl)-3H-1, 2-dithiole-3-thione(ADT-OH)with memantine through alkanes as linkers and synthesized by four-step reactions from ADT-OH. Their neuroprotection against damage induced by glutamate on HT-22 cells was evaluated by MTT method. The results indicated that these compounds markedly increased the survival rates of damaged HT-22 cells at the concentration of 1 μmol/L(P< 0. 01), which suggested that these compounds could preferably protect neurons against damage induced by glutamate.
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Recent advances have seen a surge of new ideas and technologies to aid in the detection, treatment and further understanding of glaucoma. These technologies and advances are discussed to provide information on risk-factors, diagnosis and treatment. Glaucoma has never before seen such an advance in research and therapies coming forward in to the clinical workplace. It is an exciting time for physicians and researchers alike and over the next decade will certainly see advances in early detection, efficacious treatments and neuroprotection.
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Objective To observe the effect of electroacupuncture(EA) on hippocampal structure in splenic asthenia pedo-rats.Methods A total of 15 SD male rats were randomly assigned to normal control group(n=5),model group(n=5) and EA group(n=5).Splenic asthenic syndrome model was established by intragastric administration of rhubarb and intraperitoneal injection of Reserpine for 14d.EA(1mA,3Hz/15Hz) was applied to bilateral "Zusanli"(ST 36) and "Sanyinjiao"(SP 6) for 20min,once a day for 14 days.The cellular structure of hippocampus was observed by light microscope and transmission electron microscope.Results Optical microscopic observation showed that in normal control group,the cellular nucleus was distinct,and the granular cell layer well-arranged and tight.In model group,the intracellular space was widened,and the granular cell layer was out of order in the arrangement.In EA group,the cellular nucleus and the granular cell layer were nearly normal.Results of the electronic microscope showed that cells in model group had a karyopyknosis with irregular appearance and clear incisure,and some of them presented dissolving and necrotic phenomena;and those in EA group were milder in injury,had nearly-normal nucleus with visible nucleoli and relatively-intact nuclear membrane.Regarding the cellular plasma,in comparison with rich normal organelles of control group,the mitochondria in model group were swelling,with vague,dissolved and broken cristae,while in EA group,majority of the organelles were well-kept,and slightly dissolved mitochondrial cristae found.In regard to the synaptic structure,in comparison with control group,synaptic apomorphosis and swelling mitochondria were found in model group.While in EA group,milder swelling and hydropic degeneration were seen.Different from the distinct pre-and post-synaptic membrane and synaptic vesicles of control group,the synaptic clefts and vesicles of model group were vague in the profile;while those in EA group were nearly-normal.Conclusion Electroacupuncture can effectively relieve splenasthenic syndrome induced pathohistological changes of neurons of the hippocampus in the rat.