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Objective To investigate the effect of vanillin via olfactory pathway on repetitive stereotyped behavior in autistic rats and its possible mechanism.Methods The model of autism was established by the single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 of pregnant rats.Twenty-four autism animals were adopted according to the eye opening time,body mass and behavioral test.They were randomly divided into control group and vanillin group with 12 in each group,while the saline group rats as normal control group and the blank group rats as normal blank group.The repetitive stereotyped behavioral were examined in four groups of rats and the concentration of 5-HT in the amygdala was determined by immunohistochemical stainning.Results Compared with the control group,the repetitive stereotyped behaviors of vanillin group decreased (stereotype time (113.31 ± 18.45) s vs (250.52± 13.25) s,P＜0.01) and the expression of 5-HT in amygdala increased (5-HT positive neuron number(3.42± 1.32) vs (1.32± 1.04),P＜0.05).Conclusions Vanillin via olfactory pathway can improve repetitive stereotyped behaviors of autism rats,which is associated with increased the expression of 5-HT in amygdala.
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Objective To evaluate the relieving effects of vanillin sinffing on depression-like behaviors in depressed rats and to explore the possible underlying mechanism.Methods Depression animal model established by chronic unpredictable medium intensity stress combined with isolation and destroy the olfactory bulb.The depressed rats were divided randomly into vanillin inhalation group,fluoxetine hydrochloride group,depression model group,olfactory bulbectomy with the vanillin inhalation treatment group and sham-operated group.Nervous behavioral changes had been observed at different time after the administration of 5 weeks.The concentration of brain derived neurotrophic factor(BDNF) in the brain homogenate and the positive expression of BDNF in hippocampus had been also measured.Results Two weeks after the intervention,the immobility time of vanillin group((12.78 ±7.50) s) was lower than that of the model group((57.33±32.16) s) (P＜0.05).The consumption of saccharose in vanillin group((52.88±25.18)g) was higher than that of model group((37.40±19.33) g) (P＜0.05).BDNF of the brain homogenate in vanillin group (0.54±0.13) was significantly increased compared with model group (0.36± 0.06) (P＜0.01).When compared with the OBX group (0.40±0.06),similar result was obtained.Immunohistochemistry and the average density of image analysis revealed that the expression of BNDF of hippocampal CA3 in vanillin group (0.40±0.03)was significantly increased compared with model group (0.25±0.04) and OBX group (0.28±0.03) (P＜0.01).Conclusion Vanillin inhalation significantly relieves depression-like behaviors in depression rats.The possible mechanism may increase hippocampal neurogenesis by raising brain derived neurotrophic factor in brain.
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Objective To explore the localization and expression of dopaminergic neurons in olfactory bulb of cynomolgus monkeys damaged by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).Methods Three adult cynomolgus monkeys were injected with MPTP to induce the damage of dopamine neurons ( MPTP group ) and three adult cynomolgus monkeys were as a control group .Immunohistochemical staining was performed to examine the localization and expression of dopaminergic neurons in the olfactory bulb in normal and MPTP group monkeys .The numbers of DA-positive and DARPP32-positive cells were counted and the average absorbance was measured in normal and MPTP group .Results DA and DARPP32 positive neurons were concentrated in the glomerular layer ( GL) of olfactory bulb.DA positive nerve fibers were distributed in the GL while DARPP 32 positive nerve fibers appeared in all layers , and most nerve fibers were in GL and external plexiform layers (EPL).After MPTP injury, compared with the normal control group , DA and DARPP32 positive neurons and nerve fibers decreased in MPTP group and DA neurons and nerve fibers decreased significantly . Conclusions DA neurons and nerve fibers are in the GL of cynomolgus monkey olfactory bulb .DA neurons and fibers are significantly reduced in the olfactory bulb of cynomolgus monkeys damaged by MPTP , which may be associated with the dysosmia in Parkinson ’ s disease .
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Objective To explore the practice teaching model of human anatomy through re-forming the practice teaching of system anatomy and regional anatomy. Methods Three classes of clinical medicine (5-year program) were randomly selected as reform experimental classes and the other 3 classes of the same grade were used as control classes. The teaching content of practice teach-ing was reformed in the experimental classes. In the system anatomy practice teaching, the teacher controlled the teaching process and developed the theme and requirements of each experimental class while the student completed the experiment developed by the teacher. In the regional anatomy practice teaching, students' interest in learning was stimulated by the content , which was related with the surgery, and the teacher guided students to complete the operation. In control classes, the forms of student observation as well as teacher answering questions and helping students were adopted. The student grading was divided into theoretical knowledge examination and specimen assessment and the achievement was analyzed by using a Simple Analysis of Variance (ANOVA) in SPSS 16.0. Results Compared with those of control classes, the scores of system anatomy and regional anatomy in experi-mental classes were significantly increased (80.7±5.8) vs. (67.4±17.4), (85.1±4.6) vs. (62.6± 12.4) and the theoretical scores of system anatomy were also improved significantly. But no significant difference in theoretical scores of regional anatomy was observed. Conclusions The teaching mode based on the practice teaching highlights the academic characteristics of the human anatomy, increas-es students' interest in learning and improves the effectiveness of practice teaching in human anatomy.
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Objective To determine the effect of inhaling rosemary compound essential oil on learning and memory and the expression of choline acetyl transferase (ChAT) in the CA1 region of the hippocampus in rats with vascular dementia (VD).Methods A modified 2-VO method was used to induce permanent brain hypoperfusion,and thus VD,in 60 male SD rats aged 2 months.They were then randomly divided into a normal control group (n =10),a sham-operation group (n =10),a model group (n =10),a rosemary compound essential oil group (n =10) and an edaravone group (n =10).The rosemary compound essential oil group inhaled a compound of the essential oils of rosemary,eugenol and peppermint once a day; the edaravone group was given a daily injection of edaravone injecta.Both the interventions lasted for 65 days.A water maze was used to test their learning and memory abilities.Morphological damage in the CA1 region of the hippocampus and the expression of ChAT were also observed.Results The learning and memory abilities of the model group were significantly weaker compared with the sham-operated group and the normal controls.The rats in the rosemary compound essential oil and edaravone groups were obviously better than those in the model group,but there was no significant difference between rosemary compound essential oil group and the edaravone group.The morphological damage observed in the hippocampus and striatum of the model group was significantly greater,on average,than that observed in the rosemary compound essential oil group and the edaravone group.The average number of ChAT positive units in the CA1 region of the hippocampus was significantly greater in both the rosemary compound essential oil group and the edaravone group compared with the model group,but there was no significant difference between the rosemary compound essential oil group and the edaravone group.Conclusions Inhaling rosemary compound essential oil can improve the learning and memory abilities of rats with VD caused by permanent chronic brain hypoperfusion.It decreases the damage to the neurons of the hippocampus,increases the expression of ChAT,and shows a therapeutic effect on VD,at least in rats.
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Objective To explore the mechanism of the influence on mice brain of environmental tobacco smoke. Methods After the mice were placed into the bench for 8 weeks, the region of the mice brain was localized and the expression of neurotransmitters and neurotransmitters receptors were detected by immunohistochernistry.Results ( 1 ) The expression of GABA in the mice cerebral cortex ( CC ) ( 0. 25 ± 0. 06 ) and the hippocampus (Hip) (0. 19 ± 0. 07 ) were much higher in the ETS-exposed group than that in the control group(P＜ 0. 05 ). (2)The expression of nAChR on CC(0. 31 ±0. 10) was much more in the ETS-exposed group than that in control group(P＜0.05). (3) The expression of NMDAR( Glu receptors) on the CC and striate cortex were much higher in the ETS-exposed group(0.32 ±0. 10,0.38 ±0. 14), NIC-inhaling group(0.31 ±0. 08,0.31 ± 0. 11 ) than that in control group(P＜0. 05 ). Conclusions Long-term ETS-exposed and NiC-exposed environment could change the expression of neurotransmitter and its receptors.
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Objective To investigate the effects of remifentanil postconditioning on apoptosis in hippocampal neruons in a rat model of cerebral ischemia-reperfusion(I/R)and the mechanism involved.Methods Twentyfour male SD rats weighing 250-300 g were randomly divided into 4 groups(n = 6 each): sham operation group (group S);global cerebral I/R group(group I/R);remifentanil 0.6μg·kg- 1·min-1+global cerebral I/R group (group R1)and remifentanil 1.8μg·kg-1·min-1 + global cerebral I/R group(group R2).Global cerebral ischemia was induced by 10 min occlusion of bilateral common carotid combined with hypotension.In group R1 and R2,remifentanil at 0.6 and 1.8μg·kg-1·min-1 were infused for 5 min before ischemia respectively.The cognitive function was tested with Morris water maze and step-down tests from the day 3 to day 8 after reperfusion.When Morris water maze test was finished,rat brains were removed for HE staining and determination of the expression of caspase-3 in hippocampal CA1 region by immuno-histochemistry.Apoptosis in neurons in hippocampal CA1 region was detected by TUNEL assay.Results Compared with group S,the cognitive function was significantly decreased and the number of apopotic neurons in hippocampus CA1 region increased in group I/R,R1 and R2,and the expression of caspase-3 was up-regulated in group I/R(P＜0.05).Compared with group I/R,the cognitive function was significantly increased,the expression of caspase-3 was down-regulated,and the number of apopotic neurons in hippocampus CA1 region was significantly decreased in group R1 and R2(P＜0.05).Conclusion Remifentanil postconditioning can improve the cognitive function through down-regulating caspase-3 expression and inhibiting the apoptosis in hippocampal neruons in a rat model of cerebral I/R.
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Objective To design an intramedullary nail that had the same ends and could be connected to hairline pointer and employ it to fixate mid-shaft clavicular fractures. Methods Sixty adult clavicles and five fresh adult cadaveric clavicles were employed to measure full length, angle between lateral and middle segments, angle between middle and medial segments as well as the narrowest outer and inner diameters of the clavicle. The interlocked intramedullary nail with the same structure of two ends was designed and used to fixate mid-shaft clavicular fractures. The nail was inserted in retrograde manner and locking screws could be inserted at beth ends. Results The full length, angle between lateral and middle segments, angle between middle and media] segments as well as the narrowest outer and inner diameters of the clavicle were (14.82 ± 1.15) cm, 30°, 30°, (1.00±0.16) cm and (0.50± 0. 18) cm respectively. After conversely placing guide pin from the fracture end, expanding medullary cavity and adjusting the nail, the designed nail was inserted into the medullary cavity from the distal or proximal ends of the clavicle, which was locked by interlocked screws. Conclusions Self-made nail takes advantages of less surgical invasion, visible fracture reduction and stable fracture fixation for treatment of mid-shaft clavicular fractures. While the biomechanieal properties of the nail need further investigation.
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OBJECTIVE: In recent years, available evidence from basic and clinical research on Alzheimer disease(AD) suggests that oxidation stress is involved in the occurrence and development of AD, and that antioxidant treatment can improve the intelligence of patients with AD and delay age-dependant cognitive dysfunction. Although results of basic and clinical research on the therapeutic effects of antioxidants on AD are inconsistent, a large number of available data suggest that these studies are of significance. Basic pharmacological studies on natural antioxidant TA99 series indicate that they are promising novel drugs for AD. Thereby, this study made a review of their experimental basis in the treatment of AD and existing problems.DATA SOURCES: Related articles published between January 1991 and December 2004 were searched by the computer in Medline database with such key words as Alzheimer disease, antioxidant, Ginkgo biloba extract, TA9901,acetylcholine, and senescence-accelerated mouse in different combinations and with the language limited to English. Meanwhile, related articles were alsosearched in CDMA \Wanfang database with the same key words in Chinese.STUDY SELECTION: Literature involving intervention group and control group were screened in the first trial, and then non-randomized trials were excluded and the rest were searched for the full text.DATA EXTRACTION: Of the 24 basic and clinical randomized and non-randomized trials on antioxidants in the treatment of AD collected, 17 accorded with the inclusion criteria and the other 7 were excluded.DATA SYNTHESIS: Intervention in the 17 trials emphasized the pathogenesis of AD from amyloid β proterin(Aβ) synthesis, gathering to senile plaque formation, and the enhancement of Aβ gathering and neuronal apoptosis by peroxidative injuries of free radicals. Both in vitro and in vivo studies were conducted: the effect of Aβ on neurons of different regions was observed with cell culture; transmission electromicroscope and sulfrin T (Th-T) fluorescence assay, Fuliye-transform infrared(FT-IR) spectrum apparatus, electron magnetic resonance(EPR), and round spectrum were used to detect the inhibitory effect of TA99 series on Aβ gathering and fibroplasia in vitro, as well as the influence on Aβ gathering in vivo. Senescence accelerated mouse (SAM) -P/8 was adopted to establish AD model and behavioral studies such as Morris water maze were used to investigate their effect on learning and memory. Meanwhile, the clearance of intracerebral amyloid granular deposition due to TA99 was also observed with hexamic argent staining. The effects of TA series on Aβ target and possible mechanism were fully revealed, and basic pre-clinical data collection was almost completed.CONCLUSION: TA9901 plant extractions have been proved to inhibit Aβ gathering and fibrosis, and improve learning and memory of SAM-P/8 rats. Moreover, TA9902 prepared by TA9901 combined with EGb761, another synergic herb, has an obvious anti-neurotoxic effect by inhibiting Aβ gathering, fibrosis and secondary structural changes. Further pharmacological research is needed and will have a promising prospect.
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AIM: To clarify if TA9901, a natural antioxidants, could inhibit the formation of ?-amyloid(A?) fibril when A? 1-40 were injected into cerebral cortex of rat brain, and explore the mechanism of action of TA9901 on Alzheimer disesse. METHODS: Twelve Wistar rats (250-300 g) were randomly divided into four groups ( n=3 ). (1) control group; (2) TA9901 treatment group (ip. 100 mg?kg -1 ?d -1 ); (3) Vitamin E(VE) treatment group (ip. 100 mg?kg -1 ?d -1 ); (4) PBS group. 5 ?L 0.2% A? 1-40 was immediately injected into the right side of the deep cerebral cortex of control, TA9901 and VE group rats. The animals were sacrificed at the seventh day after the injection. The sections of the rat brain that contained the injected field were examined with transmission electron microscopy and Congo red staining with polarized microscopy. RESULTS: Many depositions of high electron density were observed by electron microscopy in the field where A? 1-40 was injected. They are intimately intermingled with macrophages and astrocytes. In the field, about 10nm fibrillar structures were observed that appeared similar to the fibrils seen in senile plaque (SP) of the brain of Alzheimer disease (AD). The fields in control and VE group contained richer A? fibrils than that in TA9901 group. After the sections stained with Congo red, A? 1-40 aggregation demonstrated intense birefringence under, indication the formation of amyloid fibrils. In TA9901 group, there was a weak birefringence.CONCLUSIONS: TA9901 can inhibit the fibril formation of A? that was injected into deep cerebral cortex of rat brain, this indicates primarily that TA9901 may be a potential therapeutic drug to interfere with the progression of amyloidgenesis in AD.
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Most researchers consider that high exposure to heavy metals can result in hemorrhagic gastritis,hepatonecrosis,cancer,even death.There are many routes for heavy metals to get into human body,for instance absorption by gastrointestinal tract,cutaneous absorption etc.In this paper,the author reviewed the recent researches on brain function damage induced by heavy metals via olfactory pathway.Some heavy metals have especial affinity with brain tissue and cause functional disorder and death of nerve cells,and the mechanisms were discussed in detail.
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Objective To study the neurotoxicity of lead to mice and the mechanism. Methods Two months old(grown) and two weeks old(infancy) mice were employed, 1 ?l of 1 mol/L lead acetate was given by brain ventricle injection, 3 d, 5 d, 1 week, 2 weeks and 3 weeks after treatment with lead, the change of autonomic activities and the ability of study and memory of the mice were examined. Results The latency period of Lashley Ⅲ water maze prolonged significantly in grown group and the infancy group compared with the control groups at every time point of test. Conclusion Lead exposure can damage the function of study and memory of mice, and increase the frequency of autonomic activities of theirs.
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AIM:To gain the molecular mechanism of active ingredients of EGb 761(ginkgo flavones and ginkgo lides) for the inhibition against A?_(1-42) aggregation and fibrogenesis.METHODS:Circular dichroism spectra(CD) and FI-IR were used to curve-fit and analyze the change in A?_(1-42) second structure under A? aged condition and intervention of ginkgo flavones and ginkgo lides.RESULTS:Analysis that was made of 1700-1600 m(-1) amide-Ⅰ-band and curve fitting indicated that after 30 min to 72-incubation,increase of ?-sheet in A?_(1-42) by(18.5%),but the reduction of ?-sheet by(50.95%) and(36.09%) in 72 h incubation with ginko flavones and ginkgo lides,respectively.And increase of ?-turn by(56.56%) and(46.56%) in sane condition.CONCLUSION:Obviously,?-sheet turned into ?-turn.-CH_2 and-CH groups of ketones and alkanes engaged in A?_(1-42) molecular change.
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Aim To investigate the protective effect of pituitary adenylate cyclase activating polypeptide(PACAP)on focal cerebral ischemia reperfusion injury in rats.Methods The models of focal cerebral ischemia reperfusion in rats were established with suture-occluded method to simulate the middle cerebral artery ischemia reperfusion injury in clinic.The treatment groups were given three different dose PACAP(PACAP 10-11 mol,PACAP 10-10 mol and PACAP 10-9 mol) in 15 minutes before cerebral ischemia.PACAPs were infused into lateral cerebral ventricle by microinjector.The water content of brain,the activity of superoxide dismutase(SOD),the content of malondialdehyde(MDA) and the content of nitrogen monoxidum(NO) of the brain tissue were determined.Results Compared with NS group,the water content of brain and the concentration of MDA and NO were obviously lower in each PACAP treatment group,while the activity of SOD was elevated to different degrees.Conclusion PACAP has an obvious protective effect on ischemia-reperfusion injury of focal brain tissue in rats,in which edema-alleviating,free radicals-scavenging and lipid peroxidation-attenuating could be involved.The protective effect seems to be more clear in middle-and high-dose group than in low-dose group.
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AIM: To investigate the mechanism by which TA9902 inhibits the formation of amyloid ?-peptide (A?) fibrils. METHODS: Fourier-transform infrared spectroscopy was used to study the secondary structure changes on aging A? in vitro. RESULTS: The content of ?-pleated sheet were 46.53% in the condition of A? aged alone for 30 min. When A? aged alone for 72 h, the content of ?-pleated sheet increased about 19.4% and produced a shift of random coil toward ?-pleated sheet. TA9902 induced a significant decrease in the content of ?-pleated sheet (36.09%). CONCLUSION: TA9902 effectively diminishes the ?-pleated structural content. The effect of TA9902 on the secondary structure of aged A? is associated with inhibition of A? aggregation and fibril formation.