Changes of Monoanine Levels in Different Brain Regionsof Rat with Ventral GIobus Pailidus Injured by KainicAcid Injection

Ventral globus pallidus-injured rats by kainic acid(10 mg) were used to derter-mine the monoamine levels in four different brain regions.In this model,a great decrease of NE con-centration was observed in both hippocampus and frontal cortex compared with nonnal contro.This result hints that a damage of noradrenergic neurons in this model has occurred. DA concentrations in the four brain zones after kainic acid injection were all reduced, but only in the frontal cortex and striatum the pronounced reductions were discovered while DA turnover rates in frontal cortex, stria-tum and meddullapons were significantly reduced. These results revealed a DA metabolic disorder occurring in these regions.However,5-HT concentrations as well as DBH activity, expressed by ratio of NE/DA,showed no marked difference in this model. In our study it is found that the changes of monoamine levels in this model basically reflect those discovered in AD patients.

Temporal lobe epilepsy animal model established by stereotaxic microinjection of kainic acid

BACKGROUND： Kainic acid can be used to induce a model of epilepsy by systemic injection, such as intraperitoneal or subcutaneous injection. Individual rats have different responses to kainic acid, therefore high doses of drug are required and the success rate of model induction is low. It is necessary to develop an improved method to establish a temporal lobe epilepsy （TLE） animal model. OBJECTIVE： To explore an economic, stable and efficient method of establishing a TLE animal model. DESIGN, TIME AND SETTING： A completely randomized, controlled study. The experiments were performed in the Cellular Function Laboratory of the Physiology Department, Anhui Medical University from March to July 2007. MATERIALS： Twenty adult male Wistar rats, weighing 230-260 g, were provided by the Experimental Animal Centre of Nanjing Medical University. Kainic acid was purchased from Sigma in USA. Type SN-2 stereotaxic apparatus was made by Narishge in Japan. METHODS： Wistar rats were randomly divided into a kainic acid （KA） group （n = 12） and a normal saline （NS） group （n = 8）. For intrahippocampal microinjection, a burr hole was drilled in the skull at the following stereotaxic coordinates： anteroposterior （AP） 4.1 mm caudal to bregma; lateral （ML） 4.2 mm right lateral to the midline. Rats in the KA group were injected with 2.5 μL KA （0.4 g/L） into the center of the CA3 region, while in the NS group the same volume of NS was injected into the same site. MAIN OUTCOME MEASURES： Both groups were monitored under a video capture system for 12 weeks to record spontaneous seizures. Intracranial eletroencepholograph （IEEG） recordings in vivo were performed after the behavioral observations. After the IEEG recordings, hippocampi were processed into coronal sections. Nissl and Timm stainings were then performed to observe and confirm pathology. RESULTS： Twenty rats were involved in the final analysis. Behavioral observations： the eadiest spontaneous onset of epilepsy appeared 2 weeks after injection of KA. Eight rats had spontaneous onset of epilepsy 3-12 weeks after treatment. None of rats in the NS group had spontaneous onset of epilepsy. IEEG recordings： Epileptic-form waves, such as sharp waves and spike waves, were calculated by artificial analysis The number of epileptic-form waves in the KA group increased significantly compared to those of the NS group （P 〈 0.01）. Morphology results： In the KA group, Nissl staining and Timm staining revealed typical pathology in the hippocampal temporosphenoid lobe. In the NS group, no pathology was observed. CONCLUSION： Intrahippocampal microinjection of KA is a reliable method to establish a temporal lobe epilepsy animal model, requiring low doses of kainic acid and giving a high rate of success.

Overexpression of γ-aminobutyric acid transporter subtype I leads to susceptibility to Kainic acid-induced seizure in transgenic mice

γ-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter, and the GABAergic synaptic transmission is normally terminated by the rapid uptake through GABA transporters. With transgenic mice ubiquitously overexpressing GABA transporter subtype I (GAT1), the present study explored the pathophysiological role of GAT1 in epileptogenesis. Though displaying no spontaneous seizure activity, these mice exhibit altered electroencephalographic patterns and increased susceptibility to seizure induced by kainic acid. In addition, the GABAA receptor and glutamate transporters are up-regulated in transgenic mice, which perhaps reflects a compensatory or corrective change to the elevated level of GAT1. These preliminary findings support the hypothesis that excitatory and inhibitory neurotransmission, and seizure susceptibility can be altered by neurotransmitter transporters.

Gastrodin blocks neural stem cell differentiation into glial cells mediated by kainic acid

Kainic acid can simulate excitatory amino acids in vitro. Neural stem cells, isolated from newborn Wistar rats, were cultured in vitro and exposed to 100 4 000 #M kainic acid for 7 days to induce neuronal cell differentiation, causing the number of astrocytes to be significantly increased. Treatment with a combination of 0.5 mg/L gastrodin and kainic acid also caused the number of differentiated neurons to be significantly increased compared with treatment with kainic acid alone Experimental findings suggest that gastrodin reduces the excitability of kainic acid and induces neural stem cell differentiation into neurons.

Effects of rutin on oxidative stress in mice with kainic acid-induced seizure

Flavonoids are present in foods such as fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich foods and prevention of human disease, including neurodegenerative disorders. We assessed the effect of rutin （quercetin-3-O-rutinoside） on oxidative stress in kainic acid （KA）-induced seizure. METHODS： Thirty-six BALB/c mice were randomly divided into three groups. In the control group, saline （intra-peritoneal, i.p.） was administered for 7 d, and on the last day, KA （10 mg/kg, i.p.） was injected 30 min after administration of saline. In rutin groups, mice were pretreated with rutin （100 and 200 mg/kg, i.p.） for 7 d, and on the last day, KA （10 mg/kg, i.p.） was injected 30 min after administration of rutin. Subsequently, behavioural changes were observed in mice. Lipid peroxidation and oxidative stress were measured respectively in the early and late phases after KA-induced seizures. RESULTS： Seizure scores in the rutin groups were significantly lower than those in the control group （P 〈 0.01）. Furthermore, rutin dose-dependently inhibited the number of wet-dog shakes （WDS） （P 〈 0.05）. Malondialdehyde level in the hippocampus of the rutin groups was significantly lower than that in the hippocampus of the control group on days 1 and 21 after KA administration. In the rutin groups, the thiol levels observed on day 1 after KA administration were higher than that in the control group （P 〈 0.01）. CONCLUSION： These results indicate that rutin has potential anticonvulsant and antioxidative activities against oxidative stress in KA-induced seizure in mice.

Protective effects of gastrodine on dendritic spines in kainic acid-injured neurons

EphB2 affects neuronal cells by altering the dendritic spines. The present study analyzed the neu-roprotective effects of gastrodine by measuring EphB2 expression in rat neural cells cultured in vitro and injured by kainic acid. Gastrodine （12.5, 25, and 50 mg/L） improved morphology in kainic acid-injured neurons, reduced lactate dehydrogenase leakage, decreased neuronal apoptosis, and increased EphB2 expression in neuronal cells. A moderate dose of 25 mg/L gastrodine resulted in the most significant effects. These results suggested that gastrodine suppressed the neurotoxic effects of excitatory amino acids and provided neuroprotection by remodeling neuronal dendritic spines.

N-methyl-D-aspartate receptor subunit 1 protein expression in the hippocampus and temporal cortex of kainic acid-induced epilepsy rats

BACKGROUND： The N-methyl-D-aspartate receptor subunit 1 （NMDAR1） contributes to the incidence of epilepsy. However, the relationship between epilepsy-induced brain injury and NMDAR1 remains poorly understood. OBJECTIVE： To investigate changes in NMDAR1 protein expression in the hippocampus and temporal cortex of kainic acid-induced epilepsy rats. DESIGN, TIME AND SETFING： A randomized, controlled, animal experiment was performed at the Department of Physiology and Department of Pathology, Basic Medical College of Jilin University from March 2002 to March 2003. MATERIALS： Rabbit anti-NMDAR1 antibody was purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 80 healthy, male, Wistar rats, aged 22 weeks, were randomly assigned to sham-surgery （n = 10） and model （n = 70） groups. Epilepsy models were established by injecting kainic acid （1μL） into the right amygdala, and rats were sacrificed at 2, 6, 24, 72 hours, and 7, 15, 30 days after surgery, with 10 animals at each time point. The rats in the sham-surgery group were injected with 1μL phosphate buffered saline into the right amygdala. MAIN OUTCOME MEASURES： NMDAR1 protein expression in the hippocampus and temporal cortex at 2, 6, 24, 72 hours and 7, 15, 30 days after epilepsy was detected using immunohistochemistry and flow cytometry analysis. RESULTS： In the sham-surgery group, a few NMDARl-positive cells were distributed in the hippocampus and temporal cortex. In the model group, NMDARl-positive cells were increased in the hippocampus and temporal cortex at 2 hours following kainic acid-induced epilepsy. They were significantly increased at 6 hours, and slightly decreased at 7 days （CA3 region and temporal cortex）, but remained greater than the sham-surgery group. This continued until day 30 （P 〈 0.01 ）. In addition, there were more NMDAR1 positive cells in the hippocampal CA3 and dentate gyrus than the temporal cortex （P 〈 0.01）. CONCLUSION： In epilepsy model rats, NMDAR1 protein expression was upregulated in the hippocampus and temporal cortex, and in particular in the hippocampal CA3 and dentate gyrus. NMDAR1 may participate in epilepsy and the excitation process of the epileptic brain.

A Study of Epileptiform Hippocampal Unit Activity Induced by Intracerebroventricular Injection of Kainic Acid in Rats

Hippocampal EEG and unit activities were recorded after seizures were initiated withintracerebroventricular injection of kainic acid (KA) in rats. Three kinds of hippocampal unit re-sponses to KA were found:1. Positive units: These units were characterized by high frequency burst firing temporally coincidentwith each hippocampal EEG spike.2. Negative units: These units showed a cessation of firing during each EEG paroxysm.3. Indifferent units: These units showed no evident chanses coincident with EEG paroxysms.Most positive units were hippocampal complex spike cells which correspond histologically tohippocampal pyramidal cells, and most complex spike cells fired in positive bursts after KA treat-ment. In the early period after KA injection, the positive units were concentrated in CA3 area. It was suggested that the activities of positive units may be considered as the typical epileptiformhippocampal unit activity induced by KA, and the firing features of negative units ma be the resultof the influence of hippocampal inhibitory interneurons or the result of excessive cellulardepolarization, and that hippocampal pyramidal cells were more sensitive to the epileptogenic ef-fect of KA than hippocampal intemeurons, and some pyramidal cells in CA3, in particular,may serve as "epileptic pacemaker neurons " in KA-induced epileptogenesis.

Synthesis of both epimeric triacid ananlogs of kainic acid

A practical and cheap method for synthesis of C-4 carboxylic acid substituted kainic acid analogue 5 and its epimer 6 from trans-4-hydroxyproline is described. Using this method, more interesting intermediates and analogues could be obtained easily.

Dynamic changes of mG1uR1 mRNA expression in rat hippocampus during seizures induced by kainic acid

Objective: To investigate temporospatial changes of mG1uR1 mRNA expression in rat hippocampus during seizures induced by kainic acid. Methods: Using in situ hybridization with Dig-labeled cDNA probes to examine mG1uR1 mRNA expression. The relative number of hybridization signal was quantified by image analysis systems. EEG and behavior changes of the rats were simultaneously observed. Results: All rats of the KA-injected group exhibited severe limbic convulsions. The EEG recordings also showed electrical seizure activities. The mG1uR1 mRNA expression began to increase at 1 h after KA injection and reached its maximal level at 4 - 8 h, and then it began to decrease gradually and came to the lowest by the end of 72 h. Conclusion: The enhanced early expression of mG1uR1 mRNA in hippocampus suggested that mG1uR1 may play an important role in epilepogenesis and may be related to the subsequent neuronal damage.

Time-dependent changes of astrocytes following microinjection of kainic acid and irradiation by gamma-knife in adult rat brain

objective: Two groups of rats were microinjected with kainic acid (KA) and irradiated with gam ma knife respectively on unilateral nucleus caudate-putamen to compare the response of astrocytes. Methods: The astrocytes were identified with anti-GFAP immunohistochemical ABC method and the progress of their reaction to the 2 insults was examined from 3 h to 30 d after the lesion. Results: Both lesions could induce hyperplasia and hypertrophy of astrocytes and 2 types of GFAP-ir cells were found, one with small cell body and thin process, and the other with hypertrophic cell body and thick and long process. The timecourse of GFAP expression in the 2 groups was different. In KA microinjection group, large necrotic area was ob served in the target within 24 h. Three days later, a few astrocytes appeared around the necrosis. With in crease of the survival time, hyperplasia and hypertrophy of astrocytes began to increase. Whereas in gamma knife group, hyperplasia and hypertrophy were evident from 3 h to 7 d and necrotic dots could be seen in the target on day 14. On day 30, necrosis was tnore obvious with gradual variations in GFAP expression around the necrotic area. Conclusion: The above results indicated that GFAP could be used as a marker for CNS in jury; the difference in their timing and distribution pattern suggested different mechanisms in KA microinjec tion group and gamma-knife irradiation group.

Kainic Acid, NMDA and Bicuculline Induce Elevation in Concentrations of Glutathione and Amino Acids <i>in Vivo</i>: Biomarkers for Seizure Predisposition?

The present study was carried out to investigate the effect of NMDA, bicuculline and kainic acid (KA) on the extracellular concentration of glutathione, phosphoethanolamine (PEA) and taurine in rat hippocampus in vivo. Rats were implanted with intrahippocampal microelectrodes perfused with free-glucose Krebs-Ringer solution and allowed to recover for about 2 h. After assaying baseline concentrations of amino acids, NMDA or bicuculline was administered intrahippocampally, whereas KA was given systemically. Either treatment resulted in significant high extracellular concentrations of glutathione, but only NMDA or KA resulted in high concentrations of PEA and taurine. Interestingly, the increase in glutathione concentration due to KA was followed by a delayed increase of glutamate and PEA. Our results demonstrated that increased efflux of glutathione, a common consequence of different neuroexcitotoxic agents, occurs in vivo. Given that the agents used in the present study were also convulsunts, the implication of the findings on seizure predisposition was also considered.

Mitochondrial and nuclear damages and caspase-3 expression in the hippicampal CA3 region of rats with kainic acid induced statuse pilepticus

BACKGROUND: Some scholars believed that the neuronal injury after status epilepticus is apoptosis, the main evidence is the changes of expressions of various apoptosis related genes, such as immediate-early gene, p53 gene and genes of bcl-2 family, etc. But there is still no ultrastructural evidence for apoptosis. OBJECTIVE: To observe the ultrastructural damages of mitochondrion and nucleus and the changes of caspase expression in neurons of hippocampal CA3 region in rats with status epilepticus induced by kainic acid. DESIGN: A randomized controlled study. SETTING: Department of Anesthesiology and Department of Neurology, Qilu Hospital of Shandong University. MATERIALS: Seventy-five adult male Wistar rats of 250-300 g, clean degree, were provided by the experimental animal center of Shandong University. Kainic acid was purchased from Sigma Company (USA); rabbit anti-rat polyclonal antibody caspase-3 from Santa Cruz Company (USA). METHODS: The experiments were carried out in the Department of Anesthesiology, Qilu Hospital of Shandong University from October 2005 to February 2006. ① The 75 rats were randomly divided into experimental group (n =45) and control group (n =30). ② Model establishment, convulsion grading and the judging standards for status epilepticus: Rats in the experimental group were given intraperitoneal injection of kainic acid (10 mg/kg), and those in the control group were injected with saline of the same volume. The time of seizure was recorded and their behavioral manifestations were observed, and the seizure was terminated by intraperitoneal injection of diazepam (10 mg/kg). ③ Observation under electron microscope: At 3, 12 and 24 hours after status epilepticus respectively, bilateral hippocampal tissues were taken out, semithin sections of about 75 nm were prepared after fixation, dehydration and embedding, and then observed under H-800 transmission electron microscope. ④ Immunohistochemical detection: Bilateral hippocampi were removed at 3, 12 and 24 hours after status epilepticus respectively, the fixation, dehydration, transparence, wax immersion and embedding were performed, then serial sections of CA3 region were immunohistochemically determined by the SABC method. Leica QWinV3 image analytical software was applied, then the average number and average gray value of positive cells were calculated. MAIN OUTCOME MEASURES: Results of observation under electron microscope, that of immunohistochemical staining of neurons in hippocampal CA3 region; Comparison of number of caspase-3 positive cells and gray value. RESULTS: All the 75 Wistar rats were involved in the analysis of results. ① Results of observation under electron microscope: At 3 hours after status epilepticus, swelling crista and membranous disintegration were observed under electron microscope. At 24 hours, obvious nuclear changes occurred, and manifested as the side-aggegation of chromatins. ② Results of immunohistochemical detection: In the experimental group, the number of caspase-3 positive cells at 3 hours after status epilepticus had no obvious difference as compared with that in the control group (P > 0.05); At 12 hours, the number and gray value of caspase-3 positive cells in the experimental group were higher than those in the control group (10.49±0.68 vs. 5.33±0.43; 45.57±2.27 vs. 19.79±0.33, P < 0.05), the same results were also observed at 24 hours (37.36±0.57 vs. 5.12±0.47; 115.24±1.22 vs. 18.73±0.42, P < 0.01). CONCLUSION: In the rat models of status epilepticus induced by kainic acid, mitochondrial damage was earlier than the increase of caspase-3 expression and nuclear changes, which suggested that mitochondrion was the key link for the neuronal death after status epilepticus.

Coexistence of nitric oxide synthase with γ-aminobutyric acid during seizure induced by kainic acid in SD rats

Objective: Functional significance of NO and central inhibitory neurotransmitter γ-aminobutyric(GABA) during seizures were investigated morphorlogically. Methods: A kainate-induced complex partialseizure model was used in our experiment. Twenty SD rats were randomly divided into KA 30, 60, 90, 200min and control groups. The brain sections were stained by NADPh (nicotinamide adenine dinucleotide phosphate ) diaphorase (Nd ) histochemically, and were further stained by GABA immunohistochemically.Results: Histological and immunohistochemical study revealed that in KA groups the number of Nd and GABA-positive double labelled neurons in CA3 region, CA3 region and dentate gyms was significantly reduced,compared with the control group. Conclusion: Nd coexisted with GABA in the brain. Reduction of GABA release led to relief of GABA-ergic inhibition and in the same way, reduction of NO release weakened its negative feedback modulation. Therefore neuronal synchronous paroxysmal discharges increased. GABA and NO,both having antiepileptic action, acted through different ways or different link in the same way. NO may involve in the effect of GABA-ergic neurons and play cooperative antiepileptic action with GABA.

雷公藤甲素对KA损伤大鼠星形胶质细胞的影响

目的:观察海人藻酸(Kainic acid,KA)海马内注射后星形胶质细胞的变化及雷公藤甲素(TRP)对其的影响。方法:90只SD大鼠(200～220g)随机分为3组:右侧海马注射生理盐水后生理盐水灌胃作为对照组(NS+NS),右侧海马注射海人藻酸后生理盐水灌胃干预组(KA+NS),右侧海马注射海人藻酸后雷公藤甲素灌胃干预组(KA+TRP)。动物存活1天,3天,5天,7天,14天后免疫组织化学结合图像分析技术观察海马内星形胶质细胞形态和数目的变化。结果:(KA+NS)组海马内星形胶质细胞数目明显增多,胞体明显增大,突起变短,变粗,与(NS+NS)组相比差别具有显著性(p<0.05);(KA+TRP)组星形胶质细胞数量明显减少,胞体变小,突起变细长,与(KA+NS)组相比差别具有显著性(P<0.05)。结论:KA注射后可导致大鼠海马内星形胶质细胞的激活,雷公藤甲素对KA诱导的星形胶质细胞的活化有抑制作用。

杏仁核注射KA诱导的边缘叶发作致海马神经元凋亡及黄芩苷干预研究

目的 :建立杏仁核注射红藻氨酸 (kainicacid ,KA)诱导的大鼠边缘叶发作模型 ,检测特异性脑电活动和脑血流与海马神经元凋亡的关系 ,以及黄芩苷对神经元损伤的保护作用。 方法 :采用脑立体定位注射技术 ,杏仁核注射KA诱导癫痫发作 ,以深部电极持续记录脑电和激光多普勒血流测定仪记录局部脑血流 (regionalcerebralbloodflow ,r CBF) ,发作 1h后静脉注射 30mg/kg安定终止发作 ,TUNEL染色观察应用黄芩苷和非用药组海马神经元的变化。结果 :药物注射 15～ 2 0min后动物均有癫痫发作 ,脑电图有高频高波伏丛集棘波 ,发作终止 8h时 ,同侧海马CA3区出现TUNEL染色阳性细胞 ,2 4h达高峰 ,72h下降。黄芩苷治疗后TUNEL染色阳性细胞数明显减少。发作前后r CBF无明显变化。高频高波伏丛集棘波时程越长 ,CA3区TUNEL染色阳性细胞越多。结论 :癫痫发作导致选择性海马CA3区神经元凋亡 ,可能与特异性脑电活动有关 ,但与脑缺血无关。黄芩苷对癫痫发作导致的脑损伤有保护作用。

坎地沙坦干预KA致痫大鼠心肌细胞ERK1/2的表达及其机制

目的:探讨坎地沙坦干预后海人藻酸(KA)致痫大鼠心肌细胞细胞外信号调节激酶(ERK1/2)的表达及其机制。方法:雄性Wistar大鼠(n=105)随机分为3组:A对照组(n=35);B1-5致痫组(n=35);C1-5坎地沙坦组(n=35),1-5分别表示癫痫后0、0.5、2.0、4.0及6.0 h。采用立体定位仪下杏仁核内注射KA方法制备大鼠癫痫模型,于致痫后不同时程进行灌流固定、心肌组织的石蜡包埋、切片及免疫组织化学染色,检测不同时程心肌细胞ERK1/2表达的灰度值。结果:与对照组比较,致痫组及坎地沙坦组心肌细胞于致痫后0.5 h ERK1/2表达均开始增加(P<0.05),致痫后2 h两组大鼠心肌组织ERK1/2的表达均达到高峰(P<0.01),随后逐渐下降,致痫后6 h,两组大鼠心肌组织ERK1/2表达均回到对照组水平(P>0.05)。即致痫组及坎地沙坦干预两组大鼠心肌ERK1/2蛋白表达组间比较,坎地沙坦组ERK1/2表达较低(P<0.05)。结论:ERK1/2在KA致痫大鼠心肌细胞中表现为短时程表达增加,坎地沙坦可使心肌ERK1/2表达降低。

何首乌对KA致大鼠脑胆碱能纤维损伤的保护作用

目的 :观察海人藻酸 (KA)对大鼠脑乙酰胆碱能神经元毁损后胆碱能 (AchE)纤维的数目和形态的改变 ,以探讨何首乌 (PMT)对胆碱能纤维的保护作用及机制。方法 :采用兴奋性神经毒素海人藻酸 (KA)损伤基底前脑 (BF)Meynert核团、内侧隔核 (MS)及斜角带核 (DB) ,建立毁损模型 ,用何首乌喂饲毁损实验组 ,并使用组织化学方法显示乙酰胆碱能纤维的改变及可能的用药后保护和活化作用。结果 :何首乌喂饲组与非何首乌喂饲组相比 ,其投射到海马及大脑皮质的AChE纤维数目多 ,纤维形态无破坏 ,差异有显著性 (P <0 .0 1)。结论 :何首乌对大鼠脑胆碱能神经投射纤维有保护作用。

愈痫灵方对KA致痫大鼠海马及颞叶皮质多药耐药基因MDR1b表达的影响

目的探讨愈痫灵方对耐药性癫痫模型大鼠海马及颞叶皮质多药耐药基因MDR1b表达的影响。方法 1造模:在脑立体定位仪引导下,海马区微量进样器注入红藻氨酸(KA)1.0μL(浓度为1.0μg/μL)点燃造模,选取发作行为级别在Racines标准Ⅳ级以上者,以丙戊酸钠及卡马西平灌胃干预14 d,再次亚惊厥剂量0.5μL KA复燃,选择再次发作级别在Ⅳ级以上或持续状态大鼠,且脑电图检测有癫痫样波发放者筛选为造模成功的耐药难治性癫痫模型鼠。2分组与处理:造模成功鼠随机分为愈痫灵干预组、拉莫三嗪对照组、模型组,另设假手术对照组、空白对照组共计5组,每组12只。分别给予愈痫灵汤剂、拉莫三嗪及同等体积的蒸馏水(2 m L/d)灌胃30 d。3标本处置与检测:采用荧光实时定量聚合酶链反应(RT-PCR)的方法,分别检测海马区与颞叶皮层MDR1b的表达。结果与假手术对照组、空白对照组间比较,造模成功组海马区MDR1b的表达水平明显升高(P<0.01),颞叶皮质区差异无统计学意义(P>0.05);所有造模组的海马区MDR1b表达高于颞叶皮质,差异有统计学意义(P<0.01)。与模型组比较,愈痫灵、拉莫三嗪干预后能显著降低KA致痫鼠海马区MDR1b的表达水平(P<0.05);愈痫灵方组与拉莫三嗪组间比较,海马与颞叶皮质之间差异均无统计学意义(P>0.05);各组间颞叶皮质区MDR1b表达差异无统计学意义(P>0.05)。结论 KA造模耐药性癫痫大鼠模型海马区多药耐药基因MDR1b的表达较皮质区明显升高。愈痫灵方降低海马区MDR1b的表达,可能是其抗耐药性癫痫作用机制之一。

何首乌对KA致大鼠脑胆碱能纤维损伤的保护作用

目的 :观察海人藻酸 (KA)对大鼠脑乙酰胆碱能神经元毁损后 ACh E纤维的数目和形态的改变 ,以探讨何首乌 (PMT)对胆碱能纤维的保护作用及机制。方法 :采用兴奋性神经毒素海人藻酸 (KA)损伤基底前脑 (BF) Meynert核团 ,内侧隔核 (MS)及斜角带核 (DB) ,建立毁损模型 ,用何首乌喂饲毁损实验组 ,使用组织化学方法显示乙酰胆碱能纤维的改变及可能的用药后保护和活化作用。结果 :何首乌喂饲组 (A组 )比非何首乌喂饲组 (B组 ) ,其投射到海马及大脑皮质的 ACh E纤维数目多 ,纤维形态无破坏 ,差异有显著性 (P<0 .0 1)。结论