丙烯酰胺中毒Ola和6J鼠小脑Purkinje细胞的病理改变

目的 观察丙烯酰胺（ACR）中毒后Ola和6J鼠小脑的不同病理改变。方法 采用病理学技术对小脑Purkinje细胞进行光镜和电镜定性分析。结果光镜下小脑整个Purkinje细胞深染,形态不规则;电镜下偶见胞膜限局性膨出,内含一些管状滑面内质网,在突起的表现部分胞膜分层、变厚、上述改变仅见于6J鼠,而Ola鼠未见异常变化。结论 丙烯酰胺中毒导致6J鼠小脑Purkinje细胞病理改变,这种变化可能是产生共济失调的病理基础。     

丙烯酰胺中毒后6J鼠神经组织离子的改变

目的　观察丙烯酰胺对 6J鼠神经组织离子的影响。方法　采用化学沉淀法电子显微分析技术对 6J鼠脊髓背根神经节细胞、腓神经轴突及线粒体中的离子改变进行分析。结果　胞质中K 和Cl- 在实验组均比对照组低 ,但以第 1周组降低最明显 ,Ca 、Na 和P5 均升高 ,以Ca 升高最明显。结论　丙烯酰胺中毒后胞浆中Ca 超载但总量不变。     

丙烯酰胺中毒后小鼠脑中肌酸激酶和三磷酸腺苷含量的改变及意义

目的：探讨丙烯酰胺（ACR）中毒后脑能量代谢的改变。方法：采用酶分析法测定Ola鼠和6J鼠脑组织匀浆中肌酸激酶（CK）、三磷酸腺苷（ATP）、二磷酸腺苷（ADP）、腺苷酸（AMP）和葡萄含量。结果：Ola鼠上述指标改变轻微。6J鼠ATP水平明显降低，达1．76μmol/g，与对照组（2．53μmol/g)比较，差异有显著性（P＜0．01）；ADP和AMP增加，葡萄糖降低，脑能量负荷值降低，CK活力明显受到抑制，低达1．13μmol/g，与对照组（3．16μmol/g)比较，差异有显著性（P＜0．01），且持续到第5周不恢复。结论：ACR中毒对Ola鼠脑能量代谢影响轻微且可逆，对6J鼠产生严重影响且持续时间长；脑组织供能代偿潜能损伤重，这种能量代谢的抑制是ACR产生神经元损伤的生化基础。     

小鼠亚急性丙烯酰胺中毒的神经病理研究

小鼠经腹腔内注射丙烯酰胺每日60mg/kg,每周5次,于染毒14次后出现双后肢严重瘫痪。光镜及电镜下观察到坐骨神经、肌间神经束、脊髓后索及后外侧索神经纤维呈轴索变性,以轴索内大量神经微丝聚集为其早期病理特征,比目鱼肌出现肌纤维萎缩。病变分布符合中枢-周围性远端型轴索病(Central-Peripheral Distal Axonopathy)。中毒早期即见有神经节细胞中央染色质溶解及核偏位等病理变化,脊髓前角细胞未见异常,提示感觉神经受累较早较重。中毒极期时小鼠小脑大量浦氏细胞固缩,电镜下发现浦氏细胞胞浆中滑面内质网扩张聚集,呈洋葱皮样排列,并可见血管壁旁星形细胞终足肿胀,压闭微血管腔。     

依达拉奉对帕金森病小鼠黑质多巴胺能神经元的形态学影响

[目的]探讨依达拉奉对帕金森病（Parkinson’s disease,PD）小鼠黑质多巴胺神经元的作用,为依达拉奉临床PD治疗提供实验依据。[方法]将30只健康雄性C57BL/6小鼠随机分为对照组、模型组和治疗组,每组10只。模型组和治疗组给予腹腔注射百草枯（paraquat）和代森锰（maneb）建立PD模型,完成建模后,治疗组给予依达拉奉治疗。观察3组小鼠行为学的改变、并用免疫组织化学和体视学方法对黑质酪氨酸羟化酶阳性神经元进行计数和形态计量分析。[结果]模型组与治疗组比较,自主运动活性明显减少,差异有统计学意义（P〈0.05）;与治疗组相比,模型组黑质酪氨酸羟化酶阳性神经元数量明显降低,细胞胞体肿胀,平均截面积、平均周长和平均体积明显增大,差异均有统计学意义（P〈0.05或P〈0.01）;胞浆内染色极为浅淡,轴突减少或消失,细胞轮廓不清。[结论]依达拉奉对PD小鼠黑质多巴胺能神经元有明显的神经保护作用。     

甲基叔丁基醚对妊娠期母鼠及胎鼠脑组织的作用

目的探讨甲基叔丁基醚（MTBE）对妊娠期母鼠和胎鼠中枢神经系统的影响。方法32只健康成年昆明种小鼠于妊娠第0 d开始至妊娠结束期间,用不同浓度的MTBE[0、100、400、800 mg/（kg.bw）]进行灌胃染毒,每天一次,直到胎鼠出生。取母鼠和胎鼠脑组织在光镜和透射电镜下观察其形态结构变化。结果电镜下可见母鼠和胎鼠脑组织的神经细胞和神经胶质细胞肿胀、变性,胞浆内线粒体大多呈空泡变,嵴丢失,内质网扩张,部分细胞膜破损等改变,随剂量的增高损伤作用更为明显。结论妊娠期母鼠接触低浓度MTBE可致母鼠及胎鼠神经细胞的亚细胞结构损伤。     

叠氮化钠所致大鼠中枢神经系统的病理改变

２４只雄性大鼠以３ｍｇ／ｋｇ叠氮化钠作腹腔注射，染毒，每日６次，每次间隔０．５ｈ，连续４ｄ直至中毒。神经病理检查结果表明，叠氮化钠对脑的损伤呈双侧对称性，主要是尾－壳核。光镜下可见神经元胞浆深染，核固缩，神经纤维束疏松肿胀，重者呈网眼状。电镜下早期可见神经元胞浆疏松，继而固缩，核染色质积聚，细胞周围可见肿胀的突起。神经纤维、胶质细胞和血管也出现病变。同时用大鼠建立了一个叠氮化钠引起脑内尾－壳核损伤的动物模型，以用于中毒机理研究。     

神经生长因子治疗慢性正己烷中毒5例临床观察

神经生长因子（nerve growth factor,NGF）是神经系统重要的生物活性蛋白质,研究表明神经生长因子对中枢和周围神经元的生长、发育、正常状态的维持、损伤后的保护和轴突的有效再生都有着重要作用.正己烷是神经毒物,长期接触可引起慢性中毒,主要表现为周围神经损害,我院对收治的5例职业性慢性正己烷中毒病人给予鼠神经生长因子治疗,现报告如下.     

依达拉奉对帕金森病小鼠黑质多巴胺能神经元的形态学影响

[目的]探讨依达拉奉对帕金森病( Parkinson's disease,PD)小鼠黑质多巴胺神经元的作用,为依达拉奉临床PD治疗提供实验依据. [方法]将30只健康雄性C57BL/6小鼠随机分为对照组、模型组和治疗组,每组10只.模型组和治疗组给予腹腔注射百草枯(paraquat)和代森锰(maneb)建立PD模型,完成建模后,治疗组给予依达拉奉治疗.观察3组小鼠行为学的改变、并用免疫组织化学和体视学方法对黑质酪氨酸羟化酶阳性神经元进行计数和形态计量分析.[结果]模型组与治疗组比较,自主运动活性明显减少,差异有统计学意义(P＜ 0.05);与治疗组相比,模型组黑质酪氨酸羟化酶阳性神经元数量明显降低,细胞胞体肿胀,平均截面积、平均周长和平均体积明显增大,差异均有统计学意义(P＜0.05或P＜0.01);胞浆内染色极为浅淡,轴突减少或消失,细胞轮廓不清. [结论]依达拉奉对PD小鼠黑质多巴胺能神经元有明显的神经保护作用.     

睡眠剥夺对大鼠海马锥体细胞超微结构影响

目的研究异相睡眠剥夺对大鼠海马CA1区锥体细胞形态、超微结构及线粒体的损伤作用,以阐明其介导的海马神经元凋亡机制。方法选用成年SD大鼠随机分组,采用多平台水环境法制备睡眠剥夺模型,以尼氏（Nissl）染色法光镜下观察神经元形态,并用透射电镜进一步观察海马神经元超微结构的变化,采用免疫组织化学法测定细胞色素C的水平。结果睡眠剥夺造成海马CA1区细胞数量减少,细胞排列松散,出现大量空泡。透射电镜检测显示,海马CA1区,神经元轴突水肿明显,内质网扩张,线粒体肿胀,嵴结构模糊、紊乱,线粒体数量减少,有的呈空泡样变。胞浆内细胞色素C水平明显增高。结论睡眠剥夺造成海马CA1区线粒体损伤,释放细胞色素C,从而介导了海马神经元的凋亡。     

Pathologic processes of lumbar primary sensory neurons produced by high doses of pyridoxine in rats--morphometric and electron microscopic studies

The morphologic effects of the toxicity of high doses of pyridoxine hydrochloride (vitamin B6) on the lumbar primary sensory neurons in rats were studied. The test rats were treated with 1,200 mg/kg of pyridoxine hydrochloride by intraperitoneal injection once a day, and were sacrificed by perfusion at periods ranging from one to seven days after the injection, together with the control rats. Initial lesions consisted of eccentricity and crenation of the nucleus and vacuole formation in the cytoplasm of large dorsal root ganglion neurons, 2 days after the injection. These lesions were followed by segregation of the nucleolus, axon reaction-like changes in the cytoplasm and axonal degeneration of both peripheral axons in the sural nerve and central axons in the fasciculus gracilis. The frequency of teased myelinated fibers showing axonal degeneration during tests was significantly greater than in control 3 to 7 days after the injection. No significant difference of such frequency was found between the proximal and distal sural nerve during tests. The number of large myelinated fibers per nerve in the sural nerve, when compared with control, was preferentially decreased during tests. In the fasciculus gracilis, the decrease of the density of myelinated fibers was more pronounced in the third cervical segment than in the fifth thoracic segment. Because both peripheral and central axons were similarly affected and the initial lesions were found in the neuronal cell body, the mode of degeneration of axons in this study was regarded as "neuronopathy". By both light and electron microscopy, accumulation of mitochondria, vesicles, multilamellar and dense bodies were found in the nodal and distal paranodal axons of myelinated fibers in the sixth dorsal root ganglion on the 2nd day after the injection, which preceded the degeneration of both peripheral and central axons. Such accumulation, revealed for the first time in this study, may reflect the presence of a blockade of the axoplasmic transport in the proximal axon and cell body of the lumbar primary sensory neuron and subsequently give rise to the degeneration of both peripheral and central axons of the lumbar primary sensory neuron. The pathologic alterations at the different sites of the lumbar primary sensory neuron revealed in this study should be taken into consideration for the better understanding not only of the pathogenesis of human pyridoxine-induced sensory neuropathy, but also of other human and experimental neuropathies.     

Protective effects of vitamin E on methylmercury toxicity in the dorsal root ganglia

The protective potential of Vitamin E against methylmercury neurotoxicity was investigated by means of both light and electron microscopy. Rats were treated with a daily dosage of methylmercury (2.0 mg McHg/kg body wt), Vitamin E (50 mg Vit. E/kg body wt), both methylmercury and Vitamin E, or saline solution for 8 weeks. All animals were sacrificed by intracardial perfusion of fixative and the dorsal root ganglia (L₁-L₄) (DRG) were sampled for examination. No remarkable pathological changes were observed in animals treated with Vit. E alone. McHg-treated animals showed toxic neurological signs at 8 weeks of exposure. Both light and electron microscopy demonstrated morphological changes in the neuronal cell bodies (extensive lysosomal accumulation and destruction of Nissl substance—rough endoplasmic reticulum and polyribosomal clusters) and in the dorsal root fibers (axoplasmic degradation and myelin sheath degeneration). In contrast, the McHg/Vit. E-treated animals displayed no observable neurological signs after the same duration of McHg exposure. Pathological examination revealed full protection of the DRG neurons which showed no significant degenerative changes as did those observed in McHg-alone animals. Degenerative changes, however, were still observed in the dorsal root fibers, showing moderate changes (lysosomal and axoplasmic debris accumulation) in some axons, particularly at the regions of the Nodes of Ranvier, and destruction of the myelin sheaths. It is shown in this investigation that Vitamin E can offer significant protection against methylmercury toxicity. Under our present experimental conditions, the protective effectiveness appears to be neuronal cell body > axoplasm > myelin sheaths.     

Corn oil-induced changes in the dorsal root ganglia of rats

The effects of corn oil on rat dorsal root ganglia (DRG) were examined by both light and electron microscopy. Rats were fed corn oil via intubation 5 days per week for 7 weeks. No apparent morphological lesion was observed in the DRG by means of light microscopic examination. However, various cytological changes were revealed by electron microscopy. The most prominent change was the extensive and severe edematous condition in the interstitial space. After 7 weeks of treatment, the interstitial space between neurons and nerve fibers was distended by proteinaceous edematous fluid and collagen fibers. Distention of the intercellular space between the ganglion neurons and their surrounding satellite cell sheaths also occurred. Proliferation of the supporting cells, especially the satellite cells and Schwann cells, producing long and complex networks of cellular processes in the distended interstitial space was also evident. It is believed that chronic ingestion of corn oil by rats has an adverse effect on the endothelial system leading to an increased fluid permeability and edematous condition.     

CS2对大鼠神经组织超微结构及钙分布的影响

目的探讨ＣＳ２的神经毒作用机制。方法采用透视电镜及电镜细胞化学定位技术，观察ＳＤ雄性大鼠吸入不同浓度ＣＳ２（０、１２００、２４００ｍｇ／ｍ３）后，对大鼠脑组织及坐骨神经组织的超微结构影响及对钙分布的影响。结果ＣＳ２对大鼠脑组织的影响主要表现为核膜肿胀模糊，内质网、线粒体等细胞器溶解。对外周神经组织的影响主要表现为髓鞘疏松、散开，髓鞘内一些神经微丝断裂、聚集。对钙分布的影响表现为髓鞘及轴突内侧有较多钙块沉积。结论ＣＳ２可使神经组织超微结构及细胞内、外钙分布发生异常。     

Visualization of six unique morphological subpopulations of adult frog dorsal root ganglion neurons at the light microscopic level

Subpopulations of adult frog dorsal root ganglion (DRG) neurons respond to different physiological stimuli, and have unique biophysical and pharmacological properties. Two broad-based subpopulations of DRG neurons appear under phase optics, "large clear" and "small dark" neurons, while immunochemical and electrophysiological techniques allow identification of additional subpopulations. Nevertheless, most studies of DRG neurons involve randomly selected neurons. Under bright field illumination, we found dark and clear DRG neurons are distinctly different, with dark neurons composed of four subpopulations, each with unique numbers and distribution of bright rusty-colored cytoplasmic granules, and statistically significant difference in the soma diameter distribution. The clear neurons are granule-free, but the two subpopulations have statistically significant differences in soma size distributions. Thus, morphological criteria alone allow identification of six distinct subpopulations of DRG neurons in the light microscope, although further studies are required to determine whether they correspond to physiologically different subpopulations of sensory neurons.     

Quantitative ultrastructural evidence of myelin malformation in optic nerves of rats submitted to a multideficient diet

Pups were subjected to malnutrition by feeding the lactating mothers a multi-deficient (8% protein content) diet, known as regional basic diet (RBD), from birth up to weaning. The weanings were fed the same diet until 60 days of age. Ultrastructure of the optic nerve was analyzed at postnatal (P) day P8, P13, P21, P30 and P60. Electron microscopy revealed that at P8 the process of myelination has not started yet in neither groups. At P 13 different stages of myelination were observed and, in the experimental group, the optic nerve showed non-organized axon bundles and empty spaces. Control optic nerve at P21 exhibited axons with fully developed myelin sheath; whereas malnourished group had many axons being enveloped by myelin with anomalous alteration. These alterations were present in malnourished group at P30 and P60. Quantitative analysis showed statistically significant difference between control and malnourished groups when compared to the percentage of myelinated axons, axons with myelin anomalous alterations (MAA) and non-myelinated axons. Also, the myelin area was significantly smaller in malnourished groups when compared to control group. Finally, a high percentage of large non-myelinated fibers were found in the malnourished group. In conclusion, our results show that early malnutrition by a multideficient diet (RBD) affects permanently the optic nerve organization and myelination, indicating an impairment of nerve transmission and a probable dysfunction in the visual ability.     

Pathological effects of in utero methylmercury exposure on the cerebellum of the golden hamster: II. Residual effects on the adult cerebellum

The long-term effects of prenatal methylmercury exposure were studied in the golden hamster (Mesocricetus auratus). Pregnant animals were given either 10 mg/kg methylmercury on gestational day 10 or 2 mg/kg on gestational days 10–15. Animals from treated and control litters were sacrificed as adults and cerebella examined by light and electron microscopy. Focal areas of astrogliosis were observed in the molecular layer of treated animals. Sequellae of previous injury, characterized primarily by abundant residual bodies, were observed in the perikarya and dendrites of granule and Purkinje neurons. Degenerative change of myelinated axons was observed. Possible hypotheses for continued neuronal degeneration in prenatally exposed animals are discussed.