实验性癫癎大鼠发作后海马γ-氨基丁酸B受体亚单位的表达及其激动剂的影响

目的观察海人酸(KA)诱导的实验性癫癎(EP)大鼠发作后海马γ-氨基丁酸B受体(GABABR)亚单位mRNA表达及其激动剂巴氯芬的影响。方法运用原位杂交法检测各实验组大鼠EP发作后及巴氯芬干预后海马区GABABR亚单位GAR1a及GAR2 mRNA表达。结果KA致癎早期(6~12h)2种亚单位mRNA表达水平广泛下降,至1d仍明显低于对照组(均P<0.05),但齿状回(DG)区mRNA表达开始回升,3d后表达水平已明显高于对照组(P<0.05),而CA1与CA3区表达仍维持低水平(均P<0.05),但其表达水平渐向对照组水平恢复。巴氯芬干预后亚单位表达明显下降的时间点延迟,且表达水平明显高于非干预的致癎组(P<0.05~0.01)。结论致癎鼠2种亚单位表达下降后又上调为颞叶EP的内源性自我保护机制;巴氯芬促进2种亚单位表达,增强GABA抑制作用,有利于控制EP,为筛选针对GABABR亚单位的抗癎药提供新途径。     

钙结合蛋白与颞叶癫痫大鼠海马神经元易损性的关系研究

目的 探讨微白蛋白(Parvalbumin,PV)、钙视网膜蛋白(Calretinin,CR)、钙结合蛋白-D28K(Calbindin-D28k,CB)与颞叶癫痫大鼠海马神经元易损性的关系及在颞叶癫痫的发生发展中的作用.方法 采用氯化锂-匹罗卡品颞叶癫痫大鼠模型,应用免疫组化动态观察海马神经元内PV、CR、CB的表达.结果 实验组大鼠PV阳性中间神经元的数量在CA3区无明显变化(P>0.05);在CA1区,呈进行性下降,到7d时达最低值(P<0.01);在齿状回及门区,先进行性下降,15d时达最低值(P<0.01),30d后开始上升,到60d几乎达正常水平(P>0.05).大鼠各区CR阳性中间神经元的数量较对照组均明显下降;在CA3区,急性期和慢性期下降最明显(P<0.01);在CA1区24h组的数量最少(P<0.01);在齿状回的门区15d组的数量最低(P<0.01).CB阳性中间神经元的数量在CA3区与对照组无明显变化(P>0.05);在CA1区,6h后开始减少(P<0.05),7d后达最低值(P<0.01),然后稍有回升,但仍明显低于对照组(P<0.05);门区CB阳性中间神经元的数量较对照组增加(P<0.05).结论 氯化锂-匹罗卡品颞叶癫痫动物模型中海马内含PV、CR、CB的GABA能中间神经元存在选择性易损性,CA1区含PV、CR、CB的GABA能中间神经元的急剧减少可能诱发了颞叶癫痫的急性发作;含PV、CB的GABA能中间神经元在齿状回的改变可能在颞叶癫痫自发性复发性发作的发生和发展中扮演了非常重要的角色.     

海藻氨酸致癫癎状态大鼠海马区神经元损伤与Mg2+作用的研究

目的观察海藻氨酸(KA)诱导的癫癎状态(SE)大鼠海马神经元的形态学改变和Mg2+的神经保护作用.方法选用成年雄性Wistar大鼠75只,随机分为KA组、Mg2+组和生理盐水对照组.用KA诱导大鼠SE 3 h,Mg2+组大鼠在注射KA前腹腔内注射硫酸镁100 mg/kg,在癫癎发作终止后72 h将动物处死,分别用光镜和电镜观察海马神经元形态学改变.结果 KA组大鼠注射KA后(16.1±4.7)min出现癫癎发作,Mg2+组大鼠为(25.4±6.2)min,两组比较差异有显著性(P<0.05).KA组和Mg2+组大鼠在海马区均出现了嗜酸性神经元,Mg2+组大鼠神经元损伤程度明显低于KA组.结论 KA诱导的SE可导致海马神经元坏死,而 Mg2+作为兴奋性氨基酸拮抗剂对海马神经元具有保护作用.     

海藻氨酸致癫痫状态大鼠海马区神经元损伤与Mg^2＋作用的研究

目的观察海藻氨酸(KA)诱导的癫癎状态(SE)大鼠海马神经元的形态学改变和Mg2+的神经保护作用.方法选用成年雄性Wistar大鼠75只,随机分为KA组、Mg2+组和生理盐水对照组.用KA诱导大鼠SE 3 h,Mg2+组大鼠在注射KA前腹腔内注射硫酸镁100 mg/kg,在癫癎发作终止后72 h将动物处死,分别用光镜和电镜观察海马神经元形态学改变.结果 KA组大鼠注射KA后(16.1±4.7)min出现癫癎发作,Mg2+组大鼠为(25.4±6.2)min,两组比较差异有显著性(P<0.05).KA组和Mg2+组大鼠在海马区均出现了嗜酸性神经元,Mg2+组大鼠神经元损伤程度明显低于KA组.结论 KA诱导的SE可导致海马神经元坏死,而 Mg2+作为兴奋性氨基酸拮抗剂对海马神经元具有保护作用.     

实验性癫痫大鼠发作后海马γ-氨基丁酸B受体亚单位的表达及其激动剂的影响

目的 观察海人酸(KA)诱导的实验性癫疒间(EP)大鼠发作后海马γ-氨基丁酸B受体(GABABR)亚单位mRNA表达及其激动剂巴氯芬的影响.方法 运用原位杂交法检测各实验组大鼠EP发作后及巴氯芬干预后海马区GABABR亚单位GAR1a及GAR2 mRNA表达.结果 KA致疒间早期(6～12 h)2种亚单位mRNA表达水平广泛下降,至1 d仍明显低于对照组(均P<0.05),但齿状回(DG)区mRNA表达开始回升,3 d后表达水平已明显高于对照组(P<0.05),而CA1与CA3区表达仍维持低水平(均P<0.05),但其表达水平渐向对照组水平恢复.巴氯芬干预后亚单位表达明显下降的时间点延迟,且表达水平明显高于非干预的致疒间组(P<0.05～0.01).结论 致疒间鼠2种亚单位表达下降后又上调为颞叶EP的内源性自我保护机制;巴氯芬促进2种亚单位表达,增强GABA抑制作用,有利于控制EP,为筛选针对GABABR亚单位的抗疒间药提供新途径.     

苯甲酸雌二醇预处理的去势大鼠致(癎)前后血清雌二醇和海马组织雌激素β受体的变化

目的:分析不同剂量苯甲酸雌二醇(EB)预处理的去势大鼠以海人藻酸(kainic acid,KA)致(癎)前后血清雌二醇(E2)和海马组织雌激素β受体(ER β)的水平,探讨E2、ER β与KA之间的相关性.方法:将去势大鼠随机分为对照组(O组)、不同剂量EB干预组(O+E)、致(癎)组(O+KA)和不同剂量EB预处理致(癎)组(O+E+KA).分别利用电化学发光法与免疫印迹法检测E2浓度与海马组织ERβ表达水平的变化.结果:①除小剂量EB(25 μg·kg-1)预处理的去势大鼠血清E2水平(88.8±3.23)pmol·L-1与O组(88.49±8.31)pmol·L-1差异无统计学意义外,其余剂量EB预处理(≥EB l mg·kg-1)的各组去势大鼠血清E2浓度均明显高于O组,且E2水平随EB的增加而增高,但不影响去势大鼠海马组织ER β的表达.②癫(癎)发作的早期(癫(癎)发作后2 h内)不仅降低了癫(癎)动物血清雌激素的水平,也降低了海马组织ER β的表达,但这种降低与癫(癎)发作的轻重程度无关.结论:去势大鼠海马ER β蛋白的表达水平主要与癫(癎)发作有关,雌激素对癫(癎)发作的影响可能并不体现在其对ER β表达的影响.     

雌激素和姜黄素对海人酸杏仁核点燃大鼠行为学、脑电图及海马神经元损伤的影响

目的了解雌激素和姜黄素对海人酸(kainic acid,KA)杏仁核点燃大鼠癫痫发作的影响。方法给去势的雌性大鼠添加雌激素治疗,添加姜黄素治疗,或添加雌激素和姜黄素治疗,比较各组大鼠致痫后癫痫发作的行为学、脑电图和海马神经元损伤的变化。结果给雌激素治疗的大鼠重型发作(Racine 4/5级)评分最高,而雌激素加姜黄素治疗组评分最低(P<0.05)。脑电图的变化与行为学的改变基本一致。致痫后大鼠注射KA侧海马CA3区、CA4区可见到明显的细胞损伤,而该侧海马CA1区、齿状回区(DG)及对侧海马CA3区、CA1区及DG区神经元损害不明显。雌激素组大鼠双侧海马CA3区均出现加重的神经元损害,姜黄素组及雌激素加姜黄素组大鼠海马注射对侧CA3区存活神经元较雌激素组明显增加(P<0.01)。结论高水平的雌激素可以加重癫痫的发作,给姜黄素治疗可以减轻大鼠海马CA3区神经元损害。     

蛇床子素对癫痫大鼠电压门控钾通道Kv1.2表达的影响

目的通过检测大鼠海马区钾通道Kv1.2蛋白表达的差异,探讨蛇床子素(osthole,OST)对海人酸(KA)致痫大鼠神经元的保护作用及其机制。方法 60只SD雄性大鼠随机分成空白对照组、模型组、OST组各20只。OST组首先给予OST灌胃,对照组、模型组给予等量的生理盐水灌胃,10d后,OST组与模型组通过颈内皮下注射KA致痫,对照组经颈内皮下注射等量的生理盐水。用免疫组化法和Western blot方法检测大鼠海马CA3区瞬时外向钾离子通道Kv1.2蛋白表达。结果模型组大鼠海马CA3区Kv1.2蛋白表达水平低于空白对照组(P<0.05);OST组大鼠海马CA3区Kv1.2蛋白表达水平高于模型组(P<0.05);且与空白对照组比较无明显差异(P>0.05)。结论大鼠海马CA3区神经元Kv1.2表达减少与KA导致大鼠痫样发作有关;OST对KA致痫大鼠神经元有保护作用,其作用的发挥可能与OST可增加海马CA3区神经元Kv1.2的表达有关。     

海人酸致(癎)大鼠海马结构GABAB受体亚单位表达的研究

目的:探讨海人酸诱导大鼠颞叶癫(癎)(EP)发作后2种Y-氨基丁酸(GABA)受体亚单位GABAnR亚单位1a(GBRla)和GABABR亚单位2(GBR2)在EP发生、发展中的作用.方法:运用原位杂交及免疫组化法,检测EP发作后GABABR亚单位mRNA及蛋白在海马的表达.结果:致痫早期Cal和CA3区2种亚单位mRNA表达持续低下后逐渐增加,DG区则暂时性下降后很快回升;而免疫反应早期却未见明显改变,随后Cal和CA3区表达处于低水平,DG区和颞叶皮质表达下降后很快恢复.结论:致(癎)后2种GABAB受体亚单位基因和蛋白表达上调为颞叶EP的内源性自我保护机制.     

匹罗卡品致(癎)大鼠海马γ-氨基丁酸能中间神经元生长抑素和微清蛋白mRNA表达研究

目的 观察匹罗卡品致(癎)大鼠海马γ-氨基丁酸能中间神经元生长抑素(SS)mRNA和微清蛋白(PV)mRNA表达水平变化,拟从基因水平探讨其表达阳性γ-氮基丁酸能中间神经元在颞叶癫(癎)发生发展中的作用.方法 建立匹罗卡品致(癎)大鼠模型,采用原位杂交法检测各观察时间点海马SSmRNA和PVmRNA表达阳性神经元数目.结果 模型组大鼠海马各区γ-氨基丁酸能中间神经元SSmRNA表达水平均于出现癫(癎)持续状态后3d降低最为显著(均P=0.000),随后逐渐升高;至发病后60d,海马CA3区SSmRNA表达水平高于对照组(t=1.021,P=0.005),海马门区(t=3.211,P=0.009)和CA1区(t=1.902,P=0.048)则仍低于对照组.模型组大鼠海马门区γ-氨基丁酸能中间神经元PVmRNA表达水平于出现癫(癎)持续状态后6h开始降低,至发病后60d降低最为显著(均P=0.000);海马CA1区PVmRNA表达水平于发病后3d降低最为显著(均P=0.000),随后逐渐升高但仍低于对照组(江2.216,P=0.048);癫(癎)持续状态早期,海马CA3区PVmRNA表达水平无明显变化,至发病后7d逐渐升高且高于对照组(t=1.021,P=0.005).结论 γ-氨基丁酸能中间神经元SSmRNA和PVmRNA表达水平的下调可能在颞叶癫(癎)的发生中起重要作用,至慢性期γ-氨基丁酸能中间神经元SSmRNA和PVmRNA表达水平的恢复或上调可能与颞叶癫(癎)的发展或修复有关.γ-氨基丁酸能中间神经元数目的 变化,部分是由于其标志物mRNA表达水平的调节所致,并非神经元数目变化的唯一因素.     

Effects of Low‐Frequency Hippocampal Stimulation on Gamma‐Amino Butyric Acid Type B Receptor Expression in Pharmacoresistant Amygdaloid Kindling Epileptic Rats

Objective: To observe the effect of low‐frequency hippocampal stimulation on gamma‐amino butyric acid type B (GABA‐B) receptor expression in hippocampus pharmacoresistant epileptic rats. Materials and Methods: Sixteen pharmacoresistant epileptic rats were selected by testing their seizure response to phenytoin and phenobarbital, and they were randomly divided into a pharmacoresistant control group (PRC group, eight rats) and a pharmacoresistant stimulation group (PRS group, eight rats). Another 16 pharmacosensitive epileptic rats were served as control, also divided randomly into a pharmacosensitive control group (PSC group) and a pharmacosensitive stimulation group (PSS group). A stimulation electrode was implanted into the rats' hippocampus in the four groups. Low‐frequency hippocampal stimulation was administered twice per day for two weeks. Following these weeks of stimulation, GABA‐B receptor‐positive neurons were counted and the gray values of GABA‐B receptor expression in the rats' hippocampal tissues were measured. Results: The amygdale stimulus‐induced epileptic seizures were decreased significantly in the PRS group compared with the PRC group. The parameters of the amygdale after discharge also were improved after hippocampal stimulation. Simultaneously, the GABA‐B receptor‐positive neurons increased and the GABA‐B expression gray values decreased markedly in the PRS group compared with the PRC group. The same phenomenon also was observed between the PSS group and the PSC group. However, no significant difference was found in the GABA‐B receptor‐positive neurons and the gray values of GABA‐B between the PRS group and the PSC group. Conclusions: The low‐frequency hippocampal stimulation may inhibit the amygdale stimulus‐induced epileptic seizures and the after discharges. The antiepileptic effects of the hippocampal stimulation may be achieved partly by increasing the expression of the GABA‐B receptor.     

Parvalbumin deficiency affects network properties resulting in increased susceptibility to epileptic seizures

Networks of GABAergic interneurons are of utmost importance in generating and promoting synchronous activity and are involved in producing coherent oscillations. These neurons are characterized by their fast-spiking rate and by the expression of the Ca(2+)-binding protein parvalbumin (PV). Alteration of their inhibitory activity has been proposed as a major mechanism leading to epileptic seizures and thus the role of PV in maintaining the stability of neuronal networks was assessed in knockout (PV-/-) mice. Pentylenetetrazole induced generalized tonic-clonic seizures in all genotypes, but the severity of seizures was significantly greater in PV-/- than in PV+/+ animals. Extracellular single-unit activity recorded from over 1000 neurons in vivo in the temporal cortex revealed an increase of units firing regularly and a decrease of cells firing in bursts. In the hippocampus, PV deficiency facilitated the GABA(A)ergic current reversal induced by high-frequency stimulation, a mechanism implied in the generation of epileptic activity. We postulate that PV plays a key role in the regulation of local inhibitory effects exerted by GABAergic interneurons on pyramidal neurons. Through an increase in inhibition, the absence of PV facilitates synchronous activity in the cortex and facilitates hypersynchrony through the depolarizing action of GABA in the hippocampus.     

Region‐specific upregulation of parvalbumin‐, but not calretinin‐positive cells in the ventral hippocampus during adolescence

Animal studies have highlighted the role of the ventral hippocampus‐prefrontal cortex pathway in the acquisition of mature cortical function through refinement of GABAergic circuits during adolescence. Inhibitory GABAergic responses are mediated by highly specialized interneurons, which have distinct functional properties and are characterized by the expression of calcium binding proteins. Among these, we recently found that parvalbumin (PV)‐ and calretinin (CR)‐positive interneurons in the prefrontal cortex follow opposite developmental trajectories during the periadolescent transition period. In the present study, we asked whether interneurons expressing PV and CR in the ventral hippocampus follow similar periadolescent trajectories as seen in the prefrontal cortex. By measuring the relative abundance of these interneurons in three age groups (postnatal days (PD) 25–40, 45–55, and 60–85), we found that regions within the dorso‐ventral axis of the ventral hippocampus undergo distinct developmental trajectories in PV expression during the periadolescent transition. Specifically, the ventral subiculum displayed a dramatic increase in PV‐positive interneurons from PD25–40 to PD45–55 with an increasing rostro‐caudal gradient, whereas negligible changes were found in the dorsal and middle regions. In contrast, the number of CR‐positive interneurons in the ventral hippocampus remained unchanged across the three age groups studied. Together, these results describe for the first time that GABAergic circuits in the ventral hippocampus undergo protracted development during adolescence, in particular the PV‐positive cell population circumscribed to the ventral region of the ventral hippocampus. © 2013 Wiley Periodicals, Inc.     

Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats

Summary Post-mortem studies have provided evidence for abnormalities of the γ-aminobutyric acid (GABA)-ergic system in schizophrenia. The calcium-binding proteins (CBPs), parvalbumin (PV), calbindin (CB) and calretinin (CR) can be used as markers for specific subpopulations of GABAergic neurons in the brain. Isolation rearing of rats is a non-pharmacological, non-lesion manipulation that leads to deficits in prepulse inhibition of the startle reflex (PPI) and other behavioural and neurochemical alterations reminiscent of schizophrenia. Female rats were reared in social housing (groups of three) or singly for 11 weeks post weaning and PPI was measured. Brains were removed and hippocampal CBP – containing neurons determined following immunocytochemical staining. Compared to socially housed rats, isolated rats exhibited PPI deficits and reductions in PV and CB-immunoreactive cells in the hippocampus, with no significant change in CR. These findings demonstrate selective abnormalities of sub-populations of GABAergic interneurons in the hippocampus of isolation reared rats, which resemble the neuronal deficits seen in this region in schizophrenia.     

匹罗卡品致痫大鼠的海马PV中间神经元数目变化及其轴突出芽

目的探讨PV(parvalbumin,微清蛋白)中间神经元在颞叶癫痫的发生和痫性损伤后脑组织的自我修复中的作用。方法建立匹罗卡品致痫模型。免疫组化方法检测各时间点海马不同区域PV中间神经元的数目变化及其轴突出芽情况;结合FJB(Fluoro-Jade B)行免疫荧光双标特异性检测SE(status epilepticus,癫痫持续状态)后60 d海马不同区域PV中间神经元及其轴树突的变性情况。结果实验组海马门区及CA区域PV阳性神经元数目在SE后早期均无明显变化(P>0.05)。门区PV神经元在SE后15 d时数目下降(对照组17.1±2.67,实验组15.0±3.06,P<0.05),在SE后60 d明显下降(对照组16.6±2.75,实验组9.7±2.88,P<0.01)。海马CA1区PV中间神经元数目在SE后60 d明显增多(对照组4.1±0.86,实验组6.0±1.18,P<0.01),可见相应增多的PV阳性纤维。海马CA3区PV阳性神经元数目在SE后60d明显增多(对照组4.6±0.89,实验组6.1±1.64,P<0.01),并可见相应增多的PV阳性纤维。各亚区均未见明显亦被FJB标记的PV中间神...     

海人酸致大鼠海马结构GABA_B受体亚单位表达的研究

目的:探讨海人酸诱导大鼠颞叶癫(EP)发作后2种γ-氨基丁酸(GABA)受体亚单位GABABR亚单位1a(GBR1a)和GABABR亚单位2(GBR2)在EP发生、发展中的作用。方法:运用原位杂交及免疫组化法,检测EP发作后GABABR亚单位mRNA及蛋白在海马的表达。结果:致早期CA1和CA3区2种亚单位mRNA表达持续低下后逐渐增加,DG区则暂时性下降后很快回升;而免疫反应早期却未见明显改变,随后CA1和CA3区表达处于低水平,DG区和颞叶皮质表达下降后很快恢复。结论:致后2种GABAB受体亚单位基因和蛋白表达上调为颞叶EP的内源性自我保护机制。     

Decrease in parvalbumin-expressing neurons in the hippocampus and increased phencyclidine-induced locomotor activity in the rat methylazoxymethanol (MAM) model of schizophrenia

Treatment of rats with methylazoxymethanol (MAM) on gestational day (GD)17 disrupts corticolimbic development in the offspring (MAM-GD17 rats) and leads to abnormalities in adult MAM-GD17 rats resembling those described in schizophrenic patients. The underlying changes in specific cortical and limbic cell populations remain to be characterised. In schizophrenia, decreases in inhibitory gamma-aminobutyric acid (GABA)-containing interneurons that express the calcium-binding protein parvalbumin have been reported in the prefrontal cortex and hippocampus. In this study we analysed the expression of parvalbumin (PV), calretinin (CR) and calbindin (CB) in the prefrontal cortex and hippocampus of MAM-GD17 rats. Exposure in utero to MAM led to a significant decrease in the number of neurons expressing PV in the hippocampus, but not the prefrontal cortex. Neurons expressing CR or CB were not affected in either structure. The neurochemical changes in MAM-GD17 rats were accompagnied by increased hyperlocomotion after administration of phencyclidine (PCP), analogous to the hypersensitivity of schizophrenic patients to PCP. Therefore, the developmental MAM-GD17 model reproduces key neurochemical and behavioural features that reflect cortical and subcortical dysfunction in schizophrenia, and could be a useful tool in the development of new antipsychotic drugs.     

伽玛刀低剂量照射对致疒间大鼠海马中氨基酸递质的影响

目的观察伽玛刀低剂量照射对致疒间大鼠海马中谷氨酸(Glu)、γ-氨基丁酸(GABA)的影响,探讨伽玛刀治疗癫疒间的作用机制。方法将50只锂-匹罗卡品致疒间大鼠随机分为照射组和非照射组,各25只,另取正常大鼠25只(腹腔注射生理盐水)作为对照组。照射组大鼠进行伽玛刀低剂量照射(周边剂量20Gy),对照组和非照射组大鼠不进行伽玛刀照射。用高效液相色谱-质谱-质谱(HPLC-MS-MS)分析法检测各组大鼠海马Glu、GABA的含量。结果伽玛刀照射2周后,照射组和非照射组大鼠海马中Glu含量均高于对照组,照射组GLu含量低于非照射组,差异具有统计学意义(P0.05);照射组和非照射组GABA含量均低于对照组,照射组GABA含量高于非照射组,差异具有统计学意义(P0.05)。结论伽玛刀低剂量照射通过调节海马中Glu与GABA的平衡,以达到抗癫疒间的作用。     

Striatal interneurons expressing calretinin, parvalbumin or NADPH-diaphorase: a comparative study in the rat, monkey and human

The present study is aimed at evaluating the relative number and comparing the pattern of distribution of interneurons containing calretinin (CR), parvalbumin (PV) or NADPH-d in the striatum of rats, squirrel monkeys and humans. A series of adjacent coronal sections taken at three comparable rostrocaudal levels in the three species were treated to reveal the three neuronal markers and the density of each type of chemospecific interneurons was analyzed with a computerized image analysis system. In primates, the most abundant interneurons were those expressing CR. The ratio of CR+/PV+ neurons was approximately 2-3:1 compared to a ratio of 3-4:1 for CR+/NADPH-d+ neurons. In contrast, the most frequently encountered interneurons in the rat striatum were those expressing PV. In rodents, all three interneurons were more abundant rostrally than caudally, but CR+ neurons displayed a particularly striking rostrocaudal decreasing gradient. In monkeys and humans, the three striatal interneurons were distributed rather uniformly rostrocaudally, but CR+ and PV+ interneurons were significantly more numerous in the caudate nucleus than in the putamen in humans. In monkeys, only PV+ neurons were more abundant in the caudate nucleus than in putamen. Overall, the density of the three striatal interneurons was much higher in monkeys than in rats and humans. These results reveal important species differences in respect to the relative density and pattern of distribution of striatal interneurons. These findings should be taken into account when evaluating the effect of neurodegenerative processes on cell densities in the human striatum or when studying animal models of the such diseases.     

Selective loss and axonal sprouting of GABAergic interneurons in the sclerotic hippocampus induced by LiCl-pilocarpine

In this study, we performed immunohistochemistry for somatostatin (SS), neuropeptide Y (NPY), and parvalbumin (PV) in LiCl-pilocarpine-treated rats to observe quantitative changes and axonal sprouting of GABAergic interneurons in the hippocampus, especially in the sclerotic hippocampus. Fluoro-Jade B (FJB) was performed to detect the specific degeneration of GABAergic interneurons. Compared with age-matched control rats, there were fewer SS/NPY/PV-immunoreactive (IR) interneurons in the hilus of the sclerotic hippocampus in pilocarpine-treated rats; hilar dentritic inhibitory interneurons were most vulnerable. FJB stain revealed degeneration was evident at 2 months after status epilepticus. Some SS-IR and NPY-IR interneurons were also stained for FJB, but there was no evidence of degeneration of PV-IR interneurons. Axonal sprouting of GABAergic interneurons was present in the hippocampus of epileptic rats, and a dramatic increase of SS-IR fibers was observed throughout all layers of CA1 region in the sclerotic hippocampus. These results confirm selective loss and degeneration of a specific subset of GABAergic interneurons in specific subfields of the hippocampus. Axonal sprouting of inhibitory GABAergic interneurons, especially numerous increase of SS-IR neutrophils within CA1 region of the sclerotic hippocampus, may constitute the aberrant inhibitory circum and play a significant role in the generation and compensation of temporal lobe epilepsy.