经鼻给予神经生长因子对沙林染毒大鼠梨状皮质神经元的影响

目的 探讨经鼻给予神经生长因子(NGF)对沙林染毒大鼠脑组织梨状皮质区神经元的影响.方法 建立大鼠沙林染毒模型,常规治疗后经鼻给予NGF或生理盐水,24 h后采用HE染色和免疫组织化学染色观察梨状皮质区神经元的变化.结果 与空白对照组相比,经鼻给予生理盐水的大鼠梨状皮质区可见较多变性、坏死的神经元,神经元数量[(404.75±25.17)个/mm2]明显减少(39.44%);而经鼻给予NGF组变性、坏死的神经元较少,神经元数量[(651.94±36.02)个/mm2]减少不明显.结论 经鼻给予NGF可以减轻沙林染毒大鼠梨状皮质区损伤程度.经鼻给予NGF有可能成为针对沙林所致脑损伤的有效治疗手段.     

纹状体内注射6-羟基多巴制备帕金森病大鼠模型的实验研究

目的　研究纹状体内双靶点注射 6 -羟基多巴 (6 - OHDA)制备帕金森病大鼠模型的方法。方法　将2 2 0± 10 g雄性 Wistar大鼠随机分为 3组 :模型制备组 30只 ,假手术组 10只 ,正常对照组 10只。应用立体定向仪将6 - OHDA分两点注入大鼠右侧纹状体 ,每点 10 μg/5 μl。假手术组注射等量生理盐水。术后以阿朴吗啡检测旋转行为 ,平均每分钟逆时针旋转大于 7转者为成功模型。术后 2个月处死大鼠 ,行纹状体和黑质的 HE染色和 TH免疫组化染色 ,观察病理形态学变化。结果　 30只模型制作鼠中 ,共有 2 2只在阿朴吗啡多次注射后 ,恒定地转向左侧 ,每分大于 7转 ,为成功模型。光镜下 ,HE及 TH免疫组化染色可见模型组左侧黑质内有胞浆浓染、形状不一的 DA能神经元存在 ,数量较多 ,呈带状斜行排列。右侧 SNc区内 DA能神经元几乎消失 ,残存细胞萎缩。左右侧黑质内DA能神经元数目有显著差异 (P<0 .0 5 )。结论　纹状体内注射 6 - OHDA是一种有效的制备帕金森病模型的方法 ,模型制作成功率高。     

SB203580对液化石油气中毒大鼠神经元的保护作用

目的研究p38MAPK通路抑制剂SB203580在液化石油气中毒大鼠模型中对神经元的保护作用。方法采用大鼠液化石油气中毒模型,72只SD大鼠随机分为正常对照组、中毒组和SB203580干预组,干预组在中毒前1h腹腔注射SB203580(10mg/kg,溶于5mg/ml DMSO),动物分别于中毒后1d、3d、7d处死,观察脑组织神经元的形态变化,免疫组化方法检测脑组织p38MAPK的表达水平。结果中毒组大鼠脑组织神经元坏死,p-p38MAPK阳性细胞大量表达,干预组大鼠上述变化明显减轻(P<0.05)。结论在液化石油气中毒大鼠模型中,SB203580通过抑制p38MAPK通路减少神经元坏死,发挥神经保护作用。     

Fluoro-Jade C揭示匹罗卡品模型中梨状皮质神经元变性

目的应用Fluoro-Jade C(FJC)染色方法在小鼠匹罗卡品癫痫模型中检测梨状皮质结构中神经元的变性情况,以了解梨状皮质结构在慢性颞叶癫痫发生中的病理变化和癫痫反复发作的神经基础。方法雄性昆明小鼠10只(对照组5只,匹罗卡品处理组5只)。处理组在癫痫持续状态后3d处死处理组小鼠。在梨状皮质水平切制冠状切片,行FJC染色,在荧光显微镜下观察FJC阳性细胞的形态和在梨状皮质中的整体分布情况。结果在处理组,FJC染色的脑切片上可以很清楚地看到呈亮黄绿色荧光的FJC阳性细胞,呈神经元形态,胞体和突起均清晰显示。在梨状皮质和梨状内核内出现大量FJC阳性细胞,而对照组未见。结论在小鼠匹罗卡品癫痫模型中运用FJC染色技术显示梨状皮质内发生了大量神经元变性,此研究有利于更好地理解颞叶癫痫中中枢神经系统所发生的长期病理变化和自发反复发作的癫痫机制。     

小鼠脑组织发育期细胞增生与分化的改变(英文)

目的探讨小鼠脑组织发育期间的细胞增生与分化。方法C57/BL6小鼠分别于出生后10天(P10)、17天(P17)、24天(P24)不同脑发育期,每天注射新生细胞标记物 5- 溴脱氧尿嘧啶核苷(BrdU),连续注射7天,并分别于末次注射后四周将小鼠处死、取脑。采用免疫组化染色及免疫荧光染色分别检测细胞增生(BrdU)与细胞分化(NeuN、APC、Iba1和S100 β)。结果细胞增生随着脑组织发育快速下降,并以皮层和纹状体区细胞增生最显著。皮层在发育早期以及纹状体和海马CA区在发育各期检测到极少数为新生神经元细胞,多数分化为胶质细胞;海马齿状回以神经元细胞再生为主;胶质细胞的再生随脑组织发育的成熟而逐渐减少。结论研究证实小鼠脑组织细胞的增生、分化以及存活与发育时期、脑组织区域相关。     

Noggin参与海人酸损伤后成年大鼠海马颗粒下区颗粒细胞增殖

目的 探讨侧脑室注射海人酸(KA)致大鼠海马损伤后Noggin的表达变化及其与颗粒细胞增殖的关系.方法 健康雄性SD大鼠32只采用随机数字表法分为实验组(16只)及对照组(16只).对照组又分为生理盐水对照组和空白对照组,各8只.实验组大鼠侧脑室注射KA,生理盐水对照组注射等剂量生理盐水.空白对照组不作处理.侧脑室注射KA 1周内,尼氏染色检测海马神经元的丢失.免疫荧光染色与原位杂交的方法检测海马齿状回BrdU标记细胞与Noggin mRNA阳性细胞的变化.结果 在侧脑室注射KA致海马损伤后1周,海马CA3、CA4区神经元丢失明显.与生理盐水对照组比较,实验组海马齿状回BrdU阳性细胞升高,差异有统计学意义(P=0.006),其中注射侧较对侧更为明显.海马Noggin mRNA阳性细胞在第3天时升高,第7天时下降.结论 侧脑室注射KA致海马损伤后.成年大鼠海马齿状回颗粒细胞异常增殖可能与Noggin表达波动有关.     

鱼藤酮致大鼠脑内α-突触核蛋白的表达分布变化(英文)

目的研究鱼藤酮所致的帕金森病大鼠的脑内α-突触核蛋白(α-synuclein, ASN)分布。方法 Wistar大鼠随机分成两组,分别给予鱼藤酮和/ 或溶剂(对照组)皮下注射,4 周后取脑组织,对黑质部位HE 染色,光镜下观察Lewy小体形态;对黑质、海马、纹状体等脑区进行酪氨酸羟化酶(tyrosine hydroxylase, TH)、ASN 免疫组织化学染色。结果在对照组大鼠脑内,ASN 广泛分布于各脑区,尤其在皮质、纹状体、海马等纤维投射丰富的区域。鱼藤酮处理的大鼠脑中,黑质TH阳性多巴胺能神经元数目减少、纹状体区TH阳性纤维脱失,黑质部位可见Lewy小体样结构;ASN阳性染色在各个脑区均有增强但各个脑区增强程度不一,黑质部位神经元胞浆和胞核内均有ASN明显聚集,纹状体可见ASN聚集围绕在细胞周围。海马部位偶见ASN在胞浆中点状聚集,胞核中无明显改变。结论在鱼藤酮皮下注射导致的帕金森病大鼠的脑内,ASN在多个脑区中表达增加,而在黑质纹状体部位聚集最为明显,蛋白分布由多巴胺能神经元的突触末端向胞浆和胞核扩展。     

托吡酯对戊四氮诱导的癫痫大鼠海马神经元bc1-2、bax基因表达的调控

目的探讨托吡酯对戊四氮癫癎模型大鼠大脑的神经保护作用及可能的机制.方法成年雄性Wistar大鼠54只,随机分为正常对照组(6只);戊四氮组(24只);托吡酯预处理组(24只).癫癎发作后分别于6、12、48 h后处死取脑,进行HE染色和bcl-2、bax免疫组化染色.结果癎性发作后海马HE染色显示;戊四氮组CA1、CA3和DC区神经元变性及坏死较托吡酯预处理组显著.免疫组化染色显示托吡酯预处理组bcl-2 12和48 h在CA1、CA3和DC的表达强于戊四氮组,而bax在上述时段的表达则较戊四氮组弱.结论托吡酯具有一定的神经保护作用,推测可能与其增强大鼠海马神经元bcl-2基因表达,降低bax基因表达有关.     

急性氧化乐果中毒后脑水肿的MRI表现和病理改变对比研究

目的:建立40％氧化乐果皮下染毒急性猫中毒模型,观察急性有机磷中毒脑损害的MRI影像学表现的发生发展规律,分析影像学表现与脑组织光镜、电镜病理改变的关系。方法将健康家猫25只,分为三组,对照组、染毒治疗组、染毒未治疗组。对照组(5只):即未染毒动物。染毒治疗组(简称染毒组)(15只):腹部皮下四点等量注射40％氧化乐果0.3ml/kg。染毒后2min肌肉注射0.5mg/kg硫酸阿托品,然后视动物流涎、流泪情况酌情肌注阿托品。染毒未治疗组( 5只):腹部皮下四点等量注射40％氧化乐果0.3ml/kg。对染毒后3小时,6小时、24小时脑MRI。表现与相应时间点脑组织光镜、电镜检查结果进行对照研究。结果:40％氧化乐果皮下染毒制作猫急性中毒模型,染毒后6小时、24小时MRI图像出现脑水肿。HE染色光镜和透射电子显微镜观察,3小时开始即出现广泛水肿表现,同时存在细胞毒性水肿和血管源性水肿,三者形态学表现相符。电镜示血脑屏障出现形态学变化,延髓24小时、6小时电镜切片中观察到神经元细胞质近三角形类晶体样物质。结论:氧化乐果染毒急性脑水肿的模型成功建立,中毒后脑水肿为混合性水肿,MRI出现异常表现稍晚于病理改变。     

小鼠脑组织发育期细胞增生与分化的改变

目的探讨小鼠脑组织发育期间的细胞增生与分化。方法C57／BL6小鼠分别于出生后10天（P10）、17天（P17）、24天（P24）不同脑发育期,每天注射新生细胞标记物5一溴脱氧尿嘧啶核苷（BrdU）,连续注射7天,并分别于末次注射后四周将小鼠处死、取脑。采用免疫组化染色及免疫荧光染色分别检测细胞增生（BrdU）与细胞分化（NeuN、APC、Iba1和S100β）。结果细胞增生随着脑组织发育快速下降,并以皮层和纹状体区细胞增生最显著。皮层在发育早期以及纹状体和海马CA区在发育各期检测到极少数为新生神经元细胞,多数分化为胶质细胞;海马齿状回以神经元细胞再生为主;胶质细胞的再生随脑组织发育的成熟而逐渐减少。结论研究证实小鼠脑组织细胞的增生、分化以及存活与发育时期、脑组织区域相关。     

Regional brain glucose utilization following intrastriatal injections of kainic acid

Regional brain glucose utilization following intrastriatal injections of kainic acid (KA) was studied by [¹⁴C]deoxyglucose autoradiography. In halothane anesthetized rats intrastriatal injections of 0.5–1.9 nmol KA produced histological lesions characterized by neuronal necrosis and glial reaction which varied in volume from approximately 3 to 25 cu. mm. These lesions were restricted to the striatal injection site. Intrastriatal injections of 3.8 nmol led to large lesions in striatum but also in ipsilateral hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. Injection doses of 0.5–3.8 nmol KA produced a large increase in striatal glucose utilization within 1 h; 7 days after injections however, glucose utilization was reduced below control levels in a dose-dependent manner. In addition to striatum there were large transient increases in glucose utilization in deep layers of frontal cortex, substantia nigra pars reticulata, ventral tier nuclei of thalamus, and lateral septum. Each of these structures bear close physical or synaptic proximity to the striatal injection site. Also, structures far distant from the striatal injection site exhibited large, transient, dose-dependent increases in glucose utilization; these regions included hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. There was a close correlation between the development of areas of neuronal necrosis and a reduction in glucose utilization.These results suggest that intrastriatal injections of KA may cause metabolic and perhaps electrical activation not only of structures near of synaptically connected to the injection site, but also of far distant, but particularly ‘sensitive’ brain structures probably by diffusion of small amounts of drug. The occurence of neuronal death in limbic structures after injections of relatively high doses of KA into striatum may result from prolonged firing in those circuits which continues without the prolonged presence of KA.The use of KA as a lesioning tool requires careful histological controls. The lack of such controls renders some behavioral and pharmacological studies of KA-lesioned animals difficult to interpret.     

GABAergic and cholinergic indices in various regions of rat brain after intracerebral injections of folic acid

Unilateral lesions were induced in the substantia innominata (SI) of rats by 3 methods: electrocoagulation, 2 nmol kainic acid (KA) injection or 50–200 nmol folic acid (FA) injection. Histological examination by cresyl violet and GABA-transaminase staining and biochemical evaluation by glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) measurement were undertaken of the SI and several remote areas. Injections of FA into the SI produced much less local but more severe distant neuronal damage than did injections of KA. Both produced sustained epileptiform activity. Electrolytic lesions, on the other hand, produced only local neuronal damage and no epileptiform activity. Biochemical measurements of GAD and histochemical staining for GABA transaminase indicated many of the neurons in the distant areas affected following FA injections were GABAergic, but cholinergic neurons were relatively spared. Damage to the cortical areas was heaviest in the superficial layers. Dose-related losses were seen in GAD in a number of regions, with the most severe distant damage being in the amygdala and pyriform cortex and significant but lesser extent in the frontal, entorhinal and temporal cortices, and in the thalamus. The striatum and hippocampus were spared. The distant damage, except in the thalamus, seemed to parallel the density of cholinergic innervation from the SI as revealed by relative drops in ChAT following KA injections into the SI. Reduction in both seizure-like activity and remote damage was brought about by pretreatment of the animals with valium (20 mg/kg) or scopolamine (50 mg/kg). The protective action of scopolamine is consistent with the possibility that cholinergic neurons may mediate much of the remote damage to GABA neurons, although they themselves are little affected. Distant effects of injections of FA into the striatum were comparable in kind but much less in magnitude to those after SI injection while amygdala injections of FA did not produce significant losses in GAD in any of the regions examined.     

Local and distant neuronal degeneration following intrastriatal injection of kainic acid

After intrastriatal injection, the neurotoxin, kainic acid, was cleared from the rat forebrain in a biphasic manner with 70% eliminated within 2 hours; by 24 hours after infusion, less than 1% of the kainic acid remained in the forebrain. The kainic acid diffused into adjacent brain structures, achieving mu molar concentrations in several regions ipsilateral to the injected striatum. At various times after intrastriatal injection of 9.3 nmoles of kainic acid, the brain was serially sectioned; the sections were stained for Nissl substance with cresyl violet or for degenerating neurons with the ammoniacal silver method. Neuronal degeneration spread unevenly into contiguous structures from the central sphere in the injected striatum and affected the ipsilateral pyriform cortex and amygdala, the deep layers of the overlying cerebral cortex, and the medial aspects of the bed nucleus of the stria terminalis and of the nucleus accumbens. In half of the rats, the pyriform cortex contralateral to the side of injection also underwent degeneration. A subpopulation of pyramidal cells in layer IV of the lateral neocortex and the CA3-CA4 pyramidal cells in the ipsilateral hippocampus were selectively affected, whereas adjacent neurons remained intact. The distribution of agyrophilic fibers and terminals in subcortical structures was consistent with the degeneration of neurons of origin in the affected striatal and extrastriatal regions. Brain sections stained by the gold sublimate technique from rats perfused 20 days after injection revealed an intense astrocytic response in all areas affected by acute neuronal degeneration. Extrastriatal damage could be markedly reduced by injection of lower doses of kainic acid (2.3 nmoles) with brief anesthesia; under these conditions, however, the subpopulation of large striatal neurons were relatively resistant, as compared to the Golgi II neurons. These studies demonstrate significant and variable neuronal degeneration beyond the primary site of the lesion after intracerebral injection of kainic acid; several factors affect the pattern of degeneration, including the amount of kainic acid injected, its biological activity, its diffusion, duration of anesthesia, and variable sensitivity of neurons. Consequently, care must be exercised in the use of this neurotoxin to determine the extent and selectivity of neuronal damage, particularly with reference to neuronal vulnerability beyond the central sphere of intrinsic neuronal degeneration.     

Striatal injections of kainic acid selectively impair serial memory performance in the rat

Rats with bilateral injections of kainic acid into the striatum were trained on a schedule of either singly alternated or continuous reinforcement in a runway. Both the acquisition and the extinction rates of the kainate-treated rats did not significantly differ from those of control rats with either reinforcement schedule. However, the kainate-treated rats ran significantly more slowly than the controls, especially at the onset of the training sessions, and, in contrast to the controls, failed to show reliable speed alternation in the late trials of the sessions with reward alternation, thus indicating both a locomotor impairment and an impairment of serial memory performance. In addition to severe loss of striatal neurons, the kainate injections induced partial neuronal loss in the neocortex, globus pallidus, hippocampus, and pyriform cortex. The similarity of the kainate-induced behavioral and pathological alterations to those of Huntington's disease is discussed.     

脑室内注射乙酰胆碱受体抗体IgG对大鼠神经元凋亡及一氧化氮合酶表达的影响

目的研究乙酰胆碱受体抗体(AchRab)对大鼠脑内神经元的损害及一氧化氮合酶(NOS)在损害中所起的作用，探讨重症肌无力(MG)中枢神经系统损害的机制。方法将AchRab IgG或健康人的IgG注入大鼠侧脑室。HE染色、TUNEL法检测细胞凋亡；免疫组化方法观察大鼠皮质、海马及杏仁核神经元型一氧化氮合酶(nNOS)和诱导型一氧化氮合酶(iNOS)表达变化。结果2周后实验组皮质、海马及杏仁核凋亡细胞明显增多，对照组仅见少量凋亡。实验组皮质、海马及杏仁核nNOS神经元数目明显减少。实验组及对照组脑内细胞均来见iNOS表达。结论AchRab脑内注射可诱导神经元凋亡；损伤皮质。海马及杏仁核nNOS神经元；但未能诱导脑内细胞iNOS表达。神经元凋亡损害参与了AchRab对中枢神经损害的机制；nNOS神经元的减少，可能与MG认知功能障碍有密切关系；而神经元的损伤可能与NO的毒性作用无关。     

Biocytin injections produce selective neuronal labeling in the rat CNS.

Large injections of biocytin into the lateral ventricle or brain resulted in the labeling of particular neuronal subpopulations in the rat CNS. Localization was accomplished using the avidin-biotin-peroxidase technique. In many cases the staining of neurons was totally complete and resembled that obtained with the Golgi technique. Regions containing labeled cells included the olfactory bulb, cerebral cortex, hippocampus, amygdala, striatum, hypothalamus, superior and inferior colliculi, cerebellar cortex, and dorsal horn of the spinal cord. Only particular cell types were labeled in each of these regions. The results of this study suggest that there is selective uptake and/or retention of biocytin, or a biotinylated metabolite of biocytin, by subpopulations of CNS neurons.     

Localization of insulin-like growth factor I (IGF-I)-like immunoreactivity in the developing and adult rat brain

The cellular distribution of insulin-like growth factor I (IGF-I) immunoreactivity was examined in the rat brain from embryonic day 15 to maturity. IGF-I immunoreactivity was found in the perikarya of neurons distributed along the entire extension of the neuronal tube in all the embryonic ages studied (E15, E17, E19 and E21). In E21 animals, the majority of immunoreactive neurons was located in the olfactory bulb, cerebral cortex, hippocampus, striatum, diencephalon, mesencephalic colliculi, trigeminal ganglion and in motoneurons of the brainstem. In 10- and 20-day-old rats, in addition to the above areas, IGF-I immunoreactivity was also observed in capillary walls, ependymal cells, choroid plexus, glial cells and most fiber paths. In postnatal ages, immunoreactivity in neuronal somas mainly restricted to the cell nuclei. However, IGF-I immunoreactivity in the neuron cytoplasm was observed in 20-day-old rats treated with colchicine while fiber paths and neuronal cell nuclei were negative in these animals. In the telencephalon of 20-day-old rats injected with colchicine, the most intense immunoreactive neurons were observed in the olfactory bulb, cerebral cortex, tenia tecta, hippocampus, islands of Calleja, septal nuclei, striatum, endopyriform nucleus and amygdala. Most diencephalic nuclei, the substantia nigra, the mesencephalic colliculi, Purkinje cells in the cerebellar cortex and several nuclei in mesencephalon, pons and medulla oblongata were also immunoreactive. In adult rats injected with colchicine, IGF-I immunoreactivity was located in the same areas as in 20-day-old rats. The number of immunoreactive cells and the intensity of the staining was reduced in adult rats as compared to that found in young postnatal animals. Glial cells were negative in adults. The distribution of IGF-I in the developing and mature rat brain supports the proposed roles of this peptide as a neuromodulator and neurotrophic factor.     

Plasma corticosterone is increased and correlated with brain acetylcholine in physostigmine- but not in neostigmine-treated rats

Rats were given intraperitoneal injections of physostigmine (PHYSO), neostigmine (NEO) or saline (SAL). Either 15 or 30 min later the number and intensity of observable cholinomimetic effects (OCE) was determined, plasma was collected for corticosterone (Cst) measurement, and the cerebral cortex, striatum, hippocampus and hypothalamus were removed after microwave treatment for the measurement of tissue acetylcholine (ACh) and choline (Ch) concentrations. Plasma Cst correlated with the number of OCEs at both 15 and 30 min in both NEO- and PHYSO-treated animals. Although the number and intensity of OCE were the same in NEO- and PHYSO-treated animals 15 min after injection, plasma Cst was significantly higher in the PHYSO-treated group. ACh levels in the cortex were also increased in PHYSO- compared with NEO-treated animals 15 min after injection. Ch levels remained unchanged. Plasma Cst correlated positively with ACh levels in the cortex and striatum in PHYSO-treated rats both 15 and 30 min after injection. These data support the involvement of central cholinergic mechanisms in the regulation of the HPA axis.     

颅内不同起源肌阵挛致脑损伤的实验研究

目的 探讨颅内不同起源的肌阵挛与脑损伤的关系及其病理学特征.方法 选择GABAA受体拮抗剂SR95531在成年SD大鼠的初级运动皮层(PMC)、纹状体(CS)、丘脑网状核(NRT)以及L-5-HTP在幼年豚鼠桥脑背侧微量注射,建立皮层-丘脑轴起源和脑干起源的肌阵挛动物模型.分别在发作达峰后10 min、30 min对各组行股动脉取血以检测血清特异性神经元烯醇化酶(NSE),并留取诱导剂注射部位对侧额叶皮层及海马行HE染色及Nissl染色,TUNEL法检测细胞凋亡,免疫组化染色检测Bcl-2、Bax蛋白表达.结果 (1)PMC组、CS组和NRT组在发作达峰后30 min时血清NSE水平较对照组明显增高,差异有统计学意义(P＜0.05),其中以PMC组最明显.(2)HE染色见PMC组、CS组和NRT组额叶皮层及海马CA3区神经细胞明显变性及坏死,而桥脑背侧组未出现明显的病理学改变.Nissl染色见PMC组、CS组和NRT组额叶皮层神经细胞计数较对照组减少56.3%～66%,而桥脑背侧组无明显异常.(3)PMC组、CS组和NRT组额叶皮层和海马CA3区凋亡阳性细胞计数较对照组升高20.4～40.7倍,而桥脑背侧组凋亡阳性细胞计数无明显增加.(4)PMC组、CS组和NRT组额叶皮层和海马CA3区Bax蛋白表达均较对照组明显增高,Bcl-2蛋白表达明显降低,差异有统计学意义(P＜0.05),而桥脑背侧组与对照组比较差异无统计学意义.结论 PMC、CS和NRT等皮层-丘脑轴起源的肌阵挛发作可引起额叶皮层、海马神经细胞明显减少等组织学损伤,其损伤的发生与肌阵挛痫性放电激活神经细胞凋亡和坏死过程相关,因而属于惊厥性脑损伤.脑干起源的肌阵挛未见明显异常.

Abstract：

Objective To explore the possibility of brain damage caused by myoclonic seizures of different origins and its pathologic characteristics. Methods Fifty-six adult SD rats were randomly divided into pontine micturition center (PMC) microinjection group (n=16), corpus striatum (CS) microinjection group (n=16), reticular thalamic nucleus (RTN) microinjection group (n=16), and normal control group (n=8);24 infant Guinea Pigs were randomized into dorsal pons microinjection group (n=16) and normal control group (n=8);Models of myoclonic seizures of different origins were established by microinjecting SR95531 into the PMC, CS and NRT of adult SD rats, and microinjecting L-5-HTP into the dorsal pons of Guinea Pigs, respectively. Blood from femoral artery was drawn 10 and 30 minutes after the peak time of myoclonic seizures from PMC, CS and NRT areas of rats and from dorsal pons of Guinea Pigs to detect the level of neuron-specific enolase (NSE). All animals were sacrificed 10 and 30 minutes after the peak time of myoclonic seizures and the contralateral brain at the microinjecting sites were isolated for following study: morphology in the frontal cortex and the CA3 region of hippocampus was observed by HE staining and Nissl staining;apoptosis cells in the frontal cortex and the CA3 region of hippocampus were detected by TUNEL;protein expressions of apoptosis-related Bcl-2 and Bax were detected by immunohistochemistry. Results Significant neurodegeneration and neuronal necrosis were found by HE staining in the frontal cortex and the CA3 region of hippocampus of the myoclonus originating from PMC, CS and NRT;however, no obvious histopathologic changes were observed in the cortex of Guinea Pigs with myoclonus arising from the dorsal pons. Cell count at the frontal cortex by Nissl staining was less by 56.3%-66% (30 minutes of peak time) than that in the normal control group;however, no obvious loss of cell was observed in the cortex of the Guinea pigs with myoclonus originating from dorsal pons. The serum level of NSE was increased in all rats with myoclonus originating from PMC, CS and NRT, especially in those from PMC. TUNEL-positive cells in the frontal cortex and hippocampus caused by myoclonic seizures originating from PMC, CS and NRT were increased by 20.4-40.7 times remarkably as compared with those in the controls, but no significant increase of apoptosis cells in the Guinea pigs with myoclonus originating from dorsal pons was noted. As compared with those in the controls, significant increase of Bax protein expression and obvious decrease of Bcl-2 protein expression in the frontal cortex and hippocampus of those animals with myoclonus arising from PMC, CS and NRT were found (P<0.05);no obvious differences in those of the animals with myoclonus arising from dorsal pons were noted as compared with those of its control group (P>0.05).Conclusion The myoclonus seizure arising from the axis of cortical-thalamus but not the dorsal pons can induce the decrease of neurocytes in the susceptive area of cortex and CA3 region. The brain damage in the cortex with the myoclonic seizures originating from the axis of cortical-thalamus is caused by the epileptic discharges of myoclonus which activates the process of necrosis and apoptosis of the neurocytes in brain, which belongs to the brain injury induced by seizures. However, there is no obvious damage in cortex of the models with the myoclonus originating from the dorsal pons of Guinea Pigs.     

Benzodiazepine receptor in brain.

The evidence that the brain possesses specific receptors for benzodiazepines is summarized. Further we present a series of brain lesion experiments in rats showing that specific neuronal destructions by 6-hydroxydopamine, kainic acid in the striatum, X-ray irradiation of the hippocampus, intraperitoneal 3-acetyl-pyridine or hemisection at the thalamic level do not reduce the level of benzodiazepine receptors in striatum, hippocampus, cortex or cerebellum. These results show that the benzodiazepines are not positioned on dopamine or noradrenaline terminals, cholergic or GABA-ergic neurons in the striatum, granular cells in the hippocampus or climbing fibers in the cerebellum.