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5-HT1A Receptors On The Impact Of Epilepsy With Depression And Neurological Protection Of Research

Posted on:2012-04-05Degree:MasterType:Thesis
Country:ChinaCandidate:L TaoFull Text:PDF
GTID:2154330332496437Subject:Neurology
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Background :Epilepsy is a common disease of the nervous system, depression is oftenaccompanied by psychological barrier of patients with epilepsy, literature statistics 20-55%of epilepsy patients complicated with depression [1], 5-HT and the incidence of bothepilepsy and depression relationship, 5-HT is the nerve system, an importantneurotransmitter, involved in human perception, motion and many other physiologicalprocesses, 5-HT1A ,5-HT2C and 5-HT7 has been studied with epilepsy [2], 5-HT1Areceptor is currently with one of the most relevant depression receptor, Maris [3] andothers in a rat model of kainate confirmed 5-HT1A agonist 8-OH-DPAT significantlyprolonged latency of epileptic seizures. On 5-HT1A receptor and control of seizures aremore, but the results was varied with the selected animal model may be relevant.Lithium-pilocarpine rat model of epilepsy is an international, and the ideal model oftemporal lobe epilepsy. Terminal pathological changes depigmentation hippocampalneurons, glial cell proliferation [4]. However, there has not been reported with 8-OH-DPATin the lithium-pilocarpine model of limbic system of the hippocampus and theepilepsy-related brain pathology such as neuronal apoptosis, glial cell proliferation studies,this paper aims by 5-HT1A receptor agonist intervention can prove in the antiepilepticeffect of pathology, which further clarify the 5-HT1A receptor agonist in the role of thepathogenesis of epilepsy, epilepsy treatment of depression associated with experimentalevidence。Objective: To establish lithium-pilocarpine model of epilepsy with depression test, observethe 5-HT1A receptor agonist 8-OH-DPAT on the rat's EEG, spontaneous seizure frequencyand duration of episodes , loss of hippocampal neurons and glial cell proliferation; byforced swimming and open field of vision of the behavioral approach, quantitative PCRmethod for determination of 5-HT1A receptor expression to assess its antidepressant effect.Method: 1) the establishment of rat model of depression with epilepsy, 120 female SD ratswere given lithium - pilocarpine induced status epilepticus, termination of the survival andgood condition after the onset of spontaneous rat epilepsy, through depression as asuccessful model assessment index; 2) successful model of the rats were randomly dividedinto 5 groups: saline group, model group and drug carbamazepine group for theintervention group alone group, carbamazepine, respectively, Add the low and high dose8-OH-DPAT group. Appropriate drugs were given through the rat brain electrical activity, spontaneous epileptic episodes, Nissl and glial fibrillary acidic proteinimmunohistochemistry to observe the efficacy of antiepileptic; Through forced swimmingand open field of vision of the behavioral approach Determination of quantitative PCR, theexpression of 5-HT1A receptors to evaluate the antidepressant effect.Results (1) In the process modeling, the other Rats were induced in the status epilepticus,in addition to the saline group of 6 rats,alive and in good condition were 116, there were 95spontaneous seizures. Behavior appears as: automatic disease appears mainly tooropharyngeal complex partial seizures, tonic clonic seizure development, an hour afterstatus epilepticus onset to give stability and suspension; two days into the stationary phase,the development of two weeks repeated spontaneous seizures. After forced swimming andopen field test evaluation of depression, the experiment model control group hair dull,unresponsive, reduced activity, the level of activity within the specified time, verticalactivity decreased significantly, the central grid extension of stay, reduce the emotionalbehavior score , fixed prolonged depression in rats with epilepsy with a success rate of 25%modeling. (2) EEG and spontaneous seizures: pilocarpine group, carbamazepine groupshowed more burst of spikes, amplitude of the latter than the former down ,8-OH-DPATgroups scattered in the event of a single spike or sharp wave and the amplitude wassignificantly reduced. Episodes within a week after the administration: the treatment groupcompared with the model of spontaneous seizure frequency reduction was statisticallysignificant (P <0.05), high dose group compared with the other two treatment groups of ratssignificantly reduced seizure frequency (P < 0.05). (3) the expression of Nissl stainingResult: The survival of hippocampal neurons less Nissl reduced compare with other groups,treatment group, neurons are restored, with statistical significance (P <0.05) the treatmentgroup the number of neurons decreased in the order high dose> low dose group>carbamazepine group, low dose group and high dose group were significantly different (P<0.05). (4) The expression of GFAP results of light microscopy: immunohistochemicalpositive cells showed brown cytoplasm and processes, normal saline control group,relatively small cell bodies, stained a light, model group, the average optical density valueof the largest drug intervention group than in the model group were significantly reduced(P <0.05), in descending order: CBZ group> low-dose> high dose group, and the high dosegroup compared with the lower dose group, was statistically significant (P <0.05). (5) openfield of vision, forced swimming test: Compared with model group, CBZ group showed nosignificant change in the depression, the other two intervention groups also had animprovement of depression, lower doses of high-dose group compared with a statistically significant (P <0.05). (6) quantitative PCR results: NS group of 5-HT1A gene expressionwas the highest, PILO group of 5-HT1A gene expression at least, the high dose group,5-HT1A gene expression was higher than the low dose group, with statistical significance(P <0.05).Conclusion (1) established in this study lithium - pilocarpine seizure pattern is very closeto the human characteristics of chronic temporal lobe epilepsy, spontaneous recurrentepileptic seizures in human chronic depression, low levels of stressors for the occurrence ofdepression development mechanism and closer, can simulate the human state of depressionwith epilepsy is associated with depression in epilepsy research for an ideal animal model.(2) 8-OH-DPAT inhibited the epileptic discharge, significantly reduced the number ofspontaneous seizures, reducing neuronal damage and glial cell proliferation, hasantiepileptic effects (3) 8-OH-DPAT vision improved the open field of vision andforced swimming in rats of depression indexes, by increasing the content of 5-HT1Areceptors with antidepressant effect...
Keywords/Search Tags:Pilocarpine, epilepsy, depression, 5-HT1A receptor
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