Effects of Exposure to Aluminum on Long-term Potentiation and AMPA Receptor Subunits in Rats in vivo

Objective To explore the effects of exposure to aluminum （AI） on long-term potentiation （LTP） and AMPA receptor subunits in rats in vivo. Methods Different dosages of aluminum-maltolate complex [Al（mal）3] were given to rats via acute intracerebroventricular （i.c.v.） injection and subchronic intraperitoneal （i.p.） injection. Following AI exposure, the hippocampal LTP were recorded by field potentiation technique in vivo and the expression of AMPAR subunit proteins （GluR1 and GluR2） in both total and membrane-enriched extracts from the CA1 area of rat hippocampus were detected by Western blot assay. Results Acute AI treatment produced dose-dependent suppression of LTP in the rat hippocampus and dose-dependent decreases of GluRz and GluR2 in membrane extracts; however, no similar changes were found in the total cell extracts, which suggests decreased trafficking of AMPA receptor subunits from intracellular pools to synaptic sites in the hippocampus. The dose-dependent suppressive effects on LTP and the expression of AMPA receptor subunits both in the membrane and in total extracts were found after subchronic AI treatment, indicating a decrease in AMPA receptor subunit trafficking from intracellular pools to synaptic sites and an additional reduction in the expression of the subunits. Conclusion Al（mal）3 obviously and dose-dependently suppressed LTP in the rat hippocampal CA1 region in vivo, and this suppression may be related to both trafficking and decreases in the expression of AMPA receptor subunit proteins. However, the mechanisms underlying these observations need further investigation.

Effects of Chronic Administration of Melatonin on Spatial Learning Ability and Long-term Potentiation in Lead-exposed and Control Rats

Objective To explore the changes in spatial learning performance and long-term potentiation （LTP） which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin （MT） for two months. Methods Experiment was performed in adult male Wistar rats （12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment）. The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin （3 mg/kg） or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus （DG） area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children.

Effect of Aluminum on Long-Term Potentiation and Its Relation to L-arg-No-pathway in Hippocampal CA3 Area of Rats

Experiments were performed on 64 Sprague-Dawley rats under ure-thane anesthesia. Extracellular recording method was used to investigate the effect of aluminum (Al)microinjected into CA3 on long-term potentiation (LTP) in this area. The relationship between the inhibitory effect of Al and L-arginine-NO pathway was also studied. Microinjection of Al (0. 5 mol/L, 1 μl ) into CA3 could block the induction of LTP in CA3. Microinjection of Al (0. 5 mol/L, 1 μl) into CA3 after LTP was induced could also decrease the amplitude of population spike (PS). The inhibitory effect of Al on LTP in CA3 could be enhanced by preinjection of NG-nitro-L-arginine (0. 3 mol/L, 1 μl). Preinjection of L-arginine (0. 3 mol/L, 1 μl) into CA3 could antagonize the inhibitory effect of Al on LTP. These results suggest that Al could block the induction of LTP and decrease the amplitude of PS potentiated in CA3. The effect of Al might be antagonized by L-arginine-NO pathway.

Osthole improves synaptic plasticity in the hippocampus and cognitive function of Alzheimer's disease rats via regulating glutamate

Osthole, an effective monomer in Chinese medicinal herbs, can cross the blood-brain barrier and protect against brain injury, with few toxic effects. In this study, a rat model of Alzheimer＇s disease was established after intracerebroventricular injection of β-amyloid peptide （25-35）. Subsequently the rats were intraperitoneally treated with osthole （12.5 or 25.0 mg/kg） for 14 successive days. Results showed that osthole treatment significantly improved cognitive impairment and protected hippocampal neurons of AIzheimer＇s disease rats. Also, osthole treatment alleviated suppressed long-term potentiation in the hippocampus of Alzheimer＇s disease rats. In these osthole-treated Alzheimer＇s disease rats, the level of glutamate decreased, but there was no significant change in y-amino-butyric acid. These experimental findings suggest that osthole can improve learning and memory impairment, and increase synaptic plasticity in Alzheimer＇s disease rats. These effects of osthole may be because of its regulation of central glutamate and y-amino-butyric acid levels.

Ex Vivo Characterization of the Action of Sideritis Extract Using Electrical Activity in the Rat Hippocampus Slice Preparation

A hydroethanolic extract (20% V/V) from Herba Sideritis scardica has been recognized to positively influence cognition. The present investigation aimed at the question if this extract would be able to modify intra-hippocampal communication after oral administration of 100 mg/kg daily for one week. The glutamatergic synapse between Schaffer Collaterals and pyramidal cells can be tested by electric stimulation using single pulses or theta burst stimulation. The resulting population spike is modulated by compounds acting at the central nervous system or other preparations directly or as ex vivo approach. In this case the effect of the special extract was tested in vitro the next day after repetitive in vitro administration. Conventional recording technique in the in vitro hippocampus slice revealed an increase of the population spike in the presence of single stimuli and theta burst stimuli resulting in increased long-term potentiation. This effect was tried to modulate by several glutamate receptor antagonists, among them compounds targeting at the ionic NMDA receptor (CGS19755), AMPA receptor (NBQX), Kainate receptor (UBP301) and targeting at three metabotropic glutamate receptors (mGluR I (YM298198), mGluRII ((RS)-APICA)) and mGluRIII (MSOP). Only NBQX was able to prevent the action of the Sideritis scardica extract. Since the AMPA receptor has been related to cognition in several reports in the literature, it is concluded from this result that the positive action of Sideritis scardica extract on brain function involves a modulation of AMPA receptor dependent neurotransmission.

β-adrenergic modulation of in vivo long-term potentiation in area CA1 and its role in spatial learning in rats

Activation of b-adrenoceptors in area CA1 of the hippocampus facilitates in vitro long-term potentiation (LTP) in this region. However, it is unclear if in vivo LTP in area CA1 and hippocampus-dependent learning are subjected to b-adrenergic regulation. To address this ques-tion, we investigated the effects of the b-adrenergic agonist L-isoproterenol or antagonist DL-propranolol on in vivo LTP of area CA1 and the spatial learning in Morris water maze. In the presence of L-isoproterenol (through local infusion into area CA1), the theta-pulse stimulation with the parameter of 10 Hz, 150 pulses/train, 1 train, a frequency weakly modifying synaptic strength, induced a robust LTP, and this effect was blocked when DL-propranolol was co-administered. By contrast, the theta-pulse stimulation with the parameter of 5 Hz, 150 pulses/train, 3 trains, a fre-quency strongly modifying synaptic strength, induced a significantly smaller LTP when DL-propranolol was administered into area CA1. Accordingly, DL-propranolol impaired the spatial learning in the water maze when infused into area CA1 20 min pretraining. Compared with control rats, the DL-propranolol-treated rats showed significantly slower learning in the water maze and subsequently exhibited poor memory retention at 24-h test. These results suggest that b-adrenoceptors in area CA1 are involved in regulating in vivo synaptic plasticity of this area and are important for spatial learning.

Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise （15-22 m/min, 25-64 minutes） and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus （P = 0.04） and plasma level of total antioxidant capacity of rats exposed to lead acetate （P 〈 0.001）, and significantly decreased plasma level of malondialdehyde （P 〈 0.001）. Acute exercise only decreased the hippocampal malondialdehyde level （P = 0.09） and increased brain-derived neurotrophic factor level in the hippocampus （P = 0.66）. Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly （P = 0.99）, These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

Zhengtian Pills accelerated long term potentiation both in Schaffercollateral-CA1 and perforant path-dentate gyrus synapses

Objective: To investigate the effects of Zhengtian Pills(ZTP) on long term potentiation(LTP) both in Schaffer-CA1 in vitro and perforant path-dentate gyrus(PP-DG) synapses in vivo.Methods: Sprague-Dawley rats were randomly divided into five groups: control, positive control, migraine model, low-, and high-dose ZTP groups. Glyceryl trinitrate(10 mg/kg) was injected subcutaneously to make migraine rat model. Flunarizine(0.9 mg/kg) was set as positive control. Extracellular recording technique in vivo was used to record the effects of ZTP on LTP of PP-DG pathway in anesthetized rats; Using extracellular recording technique in vitro, the effects of ZTP on LTP of Schaffer Collateral-CA1 pathway in rat hippocampal slices were investigated.Results: Compared to the control group, ZTP(1.08 g/kg) significantly enhanced population spike amplitude in PP-DG pathway; Glyceryl trinitrate(10 mg/kg) significantly reduced population spike amplitude in PP-DG pathway; Neither ZTP(0.54 g/kg) nor Flunarizine(0.9 mg/kg) had significant effects on LTP in PP-DG pathway. Compared to the model group, ZTP(1.08 g/kg), ZTP(0.54 g/kg), and flunarizine(0.9 mg/kg) significantly enhanced population spike amplitude in PP-DG pathway. Compared to the control group, ZTP(1.08 g/kg) significantly enhanced field excitatory postsynaptic potential(fEPSP) slope in Schaffer Collateral-CA1 pathway; Glyceryl trinitrate(10 mg/kg) significantly reduced f EPSP slope in Schaffer Collateral-CA1 pathway; Neither ZTP(0.54 g/kg) nor flunarizine(0.9 mg/kg) significant effects on LTP in Schaffer Collateral-CA1 pathway, Compared to the model group, ZTP(1.08 g/kg), ZTP(0.54 g/kg), and Flunarizine(0.9 mg/kg) had significantly enhanced fEPSP slope in Schaffer Collateral-CA1 pathway.Conclusion: Combined with the previous study, the results gave a clue that the effects of ZTP on TRPV1 and hippocampal LTP or their interactions could be the important molecular mechanisms of ZTP acting as migraine and headache medication.

急、慢性铅中毒对海马CA1区长时程增强和活化的细胞外信号调节激酶2影响

目的 探讨急、慢性铅中毒对大鼠海马活化的细胞外信号调节激酶 2 (ERK2 )含量的影响及其与海马CA1区长时程增强 (LTP)的关系。方法 大鼠怀孕后分别饮用蒸馏水或 0 .2 %醋酸铅溶液 ,断乳后鼠仔则直接饮用 ,于 30d后测定LTP ,并取海马作为慢性铅中毒标本测定ERK2含量。正常 30d大鼠海马片稳定培养 2h后 ,分别用含或不含 2 0 μmol·L-1 醋酸铅的人工脑脊液孵育 ,不同时间点收集 ,作为急性铅中毒标本测定ERK2含量。用Western印迹法测定标本活化的ERK2含量。结果 高频刺激后对照组和慢性铅中毒组峰电位分别为刺激前的1 85 %和 88% ;慢性铅中毒组活化的ERK2则比对照组降低了 46 %。海马片培养中 ,对照组活化的ERK2含量基本保持不变 ,铅中毒组在 30和 60min时分别下降了 68%和 33% ,1 2 0min后恢复到正常水平。

体力运动减缓慢性应激对海马的损伤作用

为探讨体力运动对慢性应激引起的海马损伤的影响 ,在大鼠整体水平检测海马长时程增强 (long termpotentiation ,LTP)和血浆糖皮质激素 (glucocorticoids ,GCs)水平。结果发现 ,8周的跑轮运动 (wheelrunning)会明显减缓随后 2 1d的慢性束缚应激对海马齿状回 (dentategyrus ,DG)LTP的抑制 ,且可维持血浆GCs水平正常。结果提示 ,长期体力运动对海马有保护作用 ,可减缓慢性应激引起的损伤。

慢性铅暴露对在体诱导年轻大鼠海马齿状回LTP的损害作用

本文研究了慢性铅暴露对大鼠在体诱导海马ＬＴＰ的影响。对照组和实验组动物从断乳至测试止，分别饮用蒸馏水和０．２％醋酸铅溶滚。应用细胞外微电极记录单脉冲刺激穿通路纤维在海马齿状回诱发的群体锋电位（ＰＳ），测量高频刺激（ＨＦＳ）前后单脉冲刺激诱发的ＰＳ的幅值及其变化，并进行组间比较。ＨＦＳ前的基线记录显示，两组间ＰＳ的平均幅值及峰潜伏期的差异无显著意义；ＨＦＳ后，１２只对照鼠有１０只产生了ＬＴＰ，其ＰＳ平均幅值增加，为基线值的１４２．７％；１１只染铅鼠只有２只产生了ＬＴＰ，其平均幅值为基线值的１２０％，但却有７只鼠产生了ＬＴＤ，其ＰＳ平均幅值低于基线值，仅为基线值的７０％。结果表明，慢性铅暴露（血铅浓度９９．２μｇ／１００ｍｌ）可使在体海马齿状回ＬＴＰ发生率和ＬＴＰ增幅明显降低，甚至在部分动物以ＬＴＤ代替了ＬＴＰ。提示慢性铅暴露可损害ＬＴＰ的诱导和维持。

三七总皂苷对海马CA1区长时程增强效应的影响

三七总皂苷（Panaxnotoginsengsaponins,PNS）是从传统中药三七的根中提取的主要有效成分,具有改善血液循环、耐缺氧、改善记忆力、抗衰老等多方面的生理活性。本研究采用“盲法”全细胞膜片钳技术观察PNS对大鼠海马CA1区锥体神经元长时程增强效应（LTP）的影响,以分析其增强学习记忆功能的神经电生理机制。以断头法分离Wistar大鼠（3-4周）海马半脑,用切片机切出400μm厚度的海马脑片,以全细胞电压钳制方式记录CA1区锥体细胞的兴奋性突触后电流（EPSCs）,给予高频刺激HFS（100 Hz）诱导LTP,分析PNS对大鼠海马CA1区EPSCs和LTP的影响。结果表明,PNS（0.1-0.4 g·L^-1）能显著抑制EPSCs（P〈0.05）,且对海马CA1区LTP无易化作用;但PNS（0.04-0.05 g·L^-1）不影响CA1区的EPSCs基础突触传递（P〉0.05）,却可以增强HFS诱发的LTP（P〈0.05）。上述结果提示,PNS（0.04-0.05 g·L^-1）能易化海马CA1区锥体神经元的长时程增强效应,该作用应是其增进学习记忆力的神经电生理机制。

针刺对糖尿病合并脑缺血大鼠海马脑片CA1区诱发长时程增强的影响

目的:探讨针刺对糖尿病合并脑缺血大鼠海马脑片诱发长时程增强(LTP)效应的影响。方法:Wistar大鼠54只,随机分为正常对照组(Con)、糖尿病+假手术组(DM+Sham-CI)、脑缺血组(CI)、糖尿病+脑缺血组(DM+CI)、糖尿病+脑缺血+针刺组(DM+CI+Acup)。腹腔注射链脲佐菌素建立糖尿病模型,3d后双侧颈总动脉结扎再灌注2次造成脑缺血模型。针刺治疗从术后1周开始,针刺穴位为"百会"、双侧"三阴交""脾俞"或"百会"、双侧"肾俞""足三里",两组穴位交替进行,留针30min,隔日1次,共治疗15次。术后40d,采用细胞外微电极记录技术,记录大鼠海马脑片CA1区诱发群峰电位(PS),然后施以100Hz、100串的高频刺激诱发LTP。结果:糖尿病合并脑缺血大鼠海马脑片PS的形状、波幅与正常动物没有明显差异,提示其并不影响海马的基础突触传递。给予高频刺激后,Con组可见PS波幅增加、斜率增大,表现为突触传递强度和效率的增强;而DM+CI组脑片在受到高频刺激后,在所观察的60min内,9个时间点PS波幅和斜率基本表现为下降趋势,与同一时间点Con组相比差异有统计学意义(P<0.05,P<0.01);DM+CI+Acup组在给予高频率刺激后,PS波幅和斜率基本表现为上升趋势,与DM+CI组同一时间点相比差异均有统计学意义(P<0.05,P<0.01)。说明糖尿病合并脑缺血大鼠的LTP效应明显降低,而针刺可以改善这种LTP效应的下降。结论:针刺对糖尿病合并脑缺血导致的学习记忆障碍的改善作用可能是通过改善LTP效应,增强突触的可塑性来实现的。

电针对衰老模型大鼠学习记忆及海马CA1区LTP的影响

目的研究电针对D-半乳糖致衰老大鼠学习记忆障碍和海马CA1区突触传递长时程增强(LTP)效应的影响,探索电针改善学习和记忆的作用机制。方法将SD大鼠随机分为正常对照组、模型组和电针组。采用腹腔注射D-半乳糖的方法建立衰老大鼠模型;电针组选取百会和足三里穴给予大鼠电针治疗,参数设定为:3Hz,1mA,连续波。采用Morris水迷宫观察大鼠行为学变化;并采用高频刺激Schaffer侧支,然后在同侧海马CA1区诱导LTP的方法检测大鼠海马突触可塑性的变化。结果模型组与正常对照组相比水迷宫测试中的逃避潜伏期明显延长,距离百分比明显降低(P<0.05,P<0.01);而电针组与模型组相比潜伏期明显缩短,距离百分比明显增大(P<0.01)。模型组与正常对照组相比海马CA1区LTP明显受到抑制(P<0.01),而电针组能减轻D-半乳糖对海马CA1区LTP的抑制作用,明显改善突触功能的可塑性(P<0.05)。结论电针可改善由D-半乳糖致衰老大鼠学习记忆能力,其作用机制之一可能与大鼠海马CA1区LTP的提高有关。

铝对大鼠海马ERK蛋白及mRNA表达影响

目的研究慢性铝中毒对大鼠海马细胞外信号调节蛋白激酶(ERK)蛋白及mRNA表达水平的变化,探讨铝中毒对学习记忆机制的影响。方法选择断乳后Wistar大鼠,用不同浓度AlCl3的水饲养3个月。测量大鼠海马长时程增强(LTP),用改良的Takai法测定丝裂原活化蛋白激酶(MAPK)活性的变化,蛋白印迹(Western blotting)方法检测ERK1/2的蛋白含量,RT-PCR方法检测ERK2的mRNA表达。结果(1)各染铝组MAPK活性降低且与对照组比较差异有统计学意义(P<0.05);(2)ERK1/2蛋白表达的比较:①ERK2在大鼠海马中的蛋白含量高于ERK1;②染铝组ERK1/2非磷酸水平与对照组比较均有所下降(P<0.05),但染铝组之间差异无统计学意义(P>0.05);③染铝组ERK1/2磷酸化水平与对照组的比较均有下降(P<0.05),染铝组之间的差异有统计学意义(P<0.05)。(3)染铝组ERK2的mRNA表达与对照组比较明显降低,但染铝组之间差异无统计学意义(P>0.05)。结论慢性铝中毒不仅影响大鼠海马中ERK2的mRNA表达水平,同时也影响ERK1/2的蛋白表达水平的降低,造成有丝分裂原活化蛋白激酶(MAPK)活性的下降,损害LTP的形成,从而影响学习记忆功能下降。

铝暴露对大鼠海马蛋白激酶Cγ亚型影响

目的通过研究慢性铝暴露大鼠海马蛋白激酶Cγ亚型(PKCγ)的蛋白和mRNA表达的变化,观察大鼠海马CA1区长时程增强(LTP)形成,探讨铝暴露对学习记忆机制的影响。方法选择断乳后Wistar大鼠,以含有不同浓度A1Cl3的水进行饲养。3个月后,测量大鼠海马LTP,用改良的Takai法测定PKC活性的变化,蛋白印迹(Western blotting)法检测PKCγ的蛋白表达;RT-PCR检测PKCγ的mRNA表达。结果(1)各染铝组PKC活性与对照组比较均降低,差异有统计学意义(P<0.01);(2)各染铝组PKCγ蛋白表达与对照组比较有降低趋势(P<0.05);(3)各染铝组PKCγmRNA表达与对照组比较均降低(P<0.05),0.2%与0.4%,0.6%组间比较差异有统计学意义(P<0.05)。结论慢性铝暴露影响大鼠海马PKCγmRNA和PKCγ蛋白表达,使PKC活性降低,导致LTP的下降,从而影响学习记忆的功能。

2450MHz微波辐射对大鼠海马长时程增强和脑组织脂褐素的影响

目的探讨微波对学习记忆影响的作用机制。方法对海马诱发电位的长时程增强 (LTP)和脑脂褐素含量进行研究 ,用 2 4 5 0MHz微波理疗机为照射源 ,以大鼠为实验对象 ,分别采用在体海马诱发电位法和分光光度法。结果 1 0 2 5mW/cm2 强度范围内的连续微波 ,可以对弱条件刺激和强条件刺激引发的LTP的群峰电位 (PS)峰值产生抑制作用 ,并存在强度 -效应关系 ,在 2 5mW/cm2 时脂褐素含量显著高于对照组和 1 0mW/cm2 组 (P <0 .0 5 )。结论 1 0 2 5mW/cm2 强度范围内的 2 4 5 0MHz连续微波可以通过抑制海马LTP的生成和脑脂褐素含量增加 ,造成学习记忆损害。

针刺百会穴对老年大鼠吸入麻醉后认知功能障碍的影响

目的探讨针刺百会穴对老年大鼠异氟醚吸入麻醉后术后认知功能障碍(POCD)的效果及电生理机制。方法 48只老年SD大鼠分为针刺百会穴+异氟醚吸入组(AI组),单纯异氟醚吸入组(I组)及对照组(C组),每组16只。AI组与I组接受1.5%异氟醚吸入4h,C组吸入空气。麻醉7d后从3组中各抽取8只进行Morris水迷宫实验,包括定位航行实验和空间探索实验,以评估3组大鼠的空间学习记忆能力;其余大鼠进行在体电生理实验,通过比较各组高频刺激(HFS)前后海马CA1区神经元场兴奋性突触后电位(fEPSP)的幅度来评价长时程增强(LTP)的变化。结果 AI组与C组每日定位航行实验的逃避潜伏期均明显短于I组(P<0.05);I组跨台次数(5.9±2.1)较AI组(15.4±1.6)与C组(16.4±1.1)明显减少(P<0.01);电生理实验:C组在HFS后1、30min和60min的fEPSP幅度为248.2%±16.3%,217.5%±17.6%与195.8%±11.9%;I组分别为201.3%±19.7%,153.2%±13.9%,146.7%±22.8%,与C组相比显著降低(P<0.01);AI组相应时间点的fEPSP幅度为240.5%±13.8%,199.6%±11.1%与194.2%±20.2%,与I组相比有明显的升高(P<0.05)。I组HFS后fEPSP幅度明显低于AI组与C组(P<0.05);AI组与C组间两种行为学实验以及LTP实验比较,差异均无统计学意义(P>0.05)。结论异氟醚吸入麻醉可导致老年大鼠发生明显的POCD,而针刺百会穴可明显缓解异氟醚所导致的学习记忆功能障碍。

不同浓度染铅大鼠海马神经元Ca_(2+)浓度与LTP关系的研究

目的 :探讨铅对大鼠海马神经元 Ca2 +浓度的影响及其与长时程增强 (L TP)的关系。方法 :断乳后 Wistar大鼠自由饮用不同浓度醋酸铅溶液 (0 .0 15 % ,0 .10 % ,0 .15 % ) ,建立慢性染铅动物模型。高频刺激 (HFS)海马区诱发长时程变化后 ,分离海马神经元 ,测定 [Ca2 + ]i。结果 :各染铅组大鼠海马神经元 [Ca2 + ]i与对照组比较均明显增高(P <0 .0 5 ) ;血铅浓度 (3.2 8± 0 .88) μm ol/ L 以上时海马 L TP产生率下降 ,三染铅组 PS幅值均降低 ,L TP阴性组 [Ca2 + ]i 明显高于 L TP阳性组 (P <0 .0 5 )。结论 :慢性染铅可使 HFS后大鼠海马神经元 [Ca2 + ]i 升高 ,损害海马区 L TP的在体诱导 ;铅致 L TP发生率下降与海马神经元 [Ca2 + ]i

白藜芦醇预处理对大鼠局灶性脑缺血/再灌注损伤的神经保护作用

目的探讨白藜芦醇(resveratrol,Res)预处理对大鼠局灶性脑缺血/再灌注损伤的神经保护作用。方法♂SD大鼠45只,随机分为假手术组(Sham)、缺血/再灌注组(I/R)和白藜芦醇预处理缺血/再灌注组(Res+I/R),每组15只。采用线栓法行大脑中动脉阻断前脑血90min,拔出栓线实现再灌注。Res+I/R组缺血前30min腹腔注射白藜芦醇(30mg·kg-1)。再灌注后24h,用2,3,5-氯化三苯基四氮唑(TTC)染色显示梗死范围;再灌注72h后利用Morris水迷宫检测脑缺血后大鼠空间学习记忆能力,用电生理学方法检测白藜芦醇对脑缺血大鼠突触可塑性的影响。结果白藜芦醇预处理可以明显缩小脑梗死体积并改善大鼠的行为学障碍(P<0.05),在Morris水迷宫实验中Res+I/R组大鼠逃避潜伏期明显短于I/R灌注组(p<0.05),高频刺激后,I/R组海马CA1区NMDA受体依赖性的长时程增强(LTP)诱导障碍(n=5),Res+I/R组海马CA1区可诱导稳定的LTP(n=5)。结论缺血前30min白藜芦醇预处理对局灶性脑缺血/再灌注损伤具有神经保护作用,可以缩小脑梗死体积,并对大鼠的学习与记忆能力具有改善作用。