衰老时人大脑皮质超微结构的变化

用电子显微镜对10例正常老年人大脑额叶、顶叶和颞叶皮质进行了研究。发现神经元核内出现包含物,神经细胞和胶质细胞质内出现多形态的纤维性包含物,线粒体变性,胞质空泡化以及脂褐素体的沉积等。突触的变性发现为突触前、后末梢内线粒体变性,突触小泡的融合破坏。     

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.     

当归芍药散改良方对体外培养海马神经元的作用

目的探索当归芍药散改良方（ｍＤＳＳ）改善老年性痴呆鼠空间学习记忆能力的机制。方法采用体外培养的海马神经元作为模型，加入服用ｍＤＳＳ的痴呆鼠血清，观察其对神经元形态学变化的影响。结果ｍＤＳＳ可延长海马神经元的存活时间，提高存活神经元中有突起神经元所占比率，对胞体的大小没有明显影响。结论ｍＤＳＳ改善学习记忆可能与其促进海马神经元存活及突起生长有关。     

雌激素对氧糖剥夺诱导神经元损伤的保护作用

目的 探讨雌激素对氧糖剥夺诱导新生大鼠皮质神经元损伤的保护作用.方法 将培养7 d的大鼠皮质神经元随机分为3组,A组为正常对照组,B组采用氧糖剥夺/复糖复氧(OGD/R)处理,C组采用雌激素预处理加OGD/R处理,各组在OGD/R后0、1、6、12、24 h各时间点,以MTT法检测细胞活性,采用TUNEL法检测神经元凋亡情况,采用细胞免疫组化方法检测生长相关蛋白(GAP-43)、脑源性神经营养因子(BDNF)的表达.结果 ①B组的神经元细胞活性较A组明显下降,C组细胞活性明显高于B组,三组比较差异有统计学意义(P<0.05).②B组凋亡神经元细胞明显多于正常对照组,OGD/R后6、12、24 h,C组凋亡细胞数目显著少于B组,三组比较差异有统计学意义(P<0.05).③B组GAP-43、BDNF的表达较正常对照组明显增加,OGD/R后6、12、24 h,C组GAP-43、BDNF表达较B组明显增加.结论 雌激素可明显提高OGD/R后神经元的存活率,使GAP-43、BDNF表达增加,抑制神经元凋亡,实现神经元损伤的保护作用. Abstract： Objective To explore the protective effects of estrogen on injury induced by OGD/R(oxygen-glucose deprivation/rehabilitation of oxygen-glucose) in neonatal rats.Methods Cortical neurons cultured for 7 days were randomly divided into group A (normal control group),group B (OGD/R, alone) and group C (pretreatment with estrogen-17βE2,and OGD/R). Then detect cell survival rate by MTT colorimetry, count the apoptotic neurons by TUNEL, observe the expression of growth associated protein(GAP-43), brain-derived neurotrophic factor (BDNF) using immunocytochemical on each time point after OGD/R 0,1, 6, 12, 24 h of each group. Results ①Compared with group A, the cell survival rate in group B decreased, the survival rate was increased in group C due to pretreatment of estrogen. ②The apoptotic neurons in group B were more than those in group A, and it was less in the group C than in group B after OGD/R 6,12,24 h. ③The expression of GAP-43, BDNF was increased in group B,and it was higher in group C than group B after OGD/R 6,12,24 h. Conclusions The study indicated that estrogen could improve the survival rate of neurons after OGD/R, increase expressions of GAP-43, BDNF,inhabit neurocyte apoptosis,and these mechanisms play neuroprotective effects.     

Prenatal exposure to diclofenac sodium changes the morphology of the male rat cervical spinal cord: a stereological and histopathological study

Diclofenac sodium is one of the most commonly used non-steroidal anti-inflammatory drugs. It may cause alteration in the nervous system during neuronal development. However, there is no investigation concerning its role in the cervical spinal cord. Pregnant rats were divided into two groups, namely drug-treated and control (saline-injected) groups. To obtain the offspring of the drug-treated group, a dose of 1 mg/kg daily diclofenac sodium (Voltaren, 75 mg/3 ml ampoule, Novartis) was injected into the pregnant rats beginning from the 5th day after mating to the 20th day of the pregnancy. To obtain the control group of offspring, serum physiological at a 1 ml/kg daily dose was injected into the pregnant control rats during the same period. Male offspring were obtained after delivery and each group was divided into two subgroups: 4-week-old and 20-week-old. The total neuron number in diclofenac sodium-treated rats was significantly lower than in the control group animals. The total volume of the cervical spinal cord segments (C1-C4) was also estimated. There was a significant difference between the volumes of the two groups, especially in the 20-week-old subgroup. This may suggest that development of neurons and volume of cervical spinal cord are affected in prenatal animals after administration of diclofenac sodium.     

新生大鼠视网膜神经元的改良培养及鉴定

目的探讨新生大鼠视网膜神经元获取和体外培养的方法,为视网膜神经细胞的基础研究提供合适的模型。方法采用酶消化法获取生后7—8天的SD（Sprague—Dawley）乳鼠的视网膜神经细胞,使用DMEM／F12培养液在体外培养,倒置显微镜观察细胞形态,免疫组织化学鉴定细胞类型。结果0．25％胰蛋白酶和0．02％EDTA联合消化能使视网膜神经细胞分散,获得单细胞悬液;多聚赖氨酸包被培养皿有助于神经细胞贴壁生长;体外培养第7天的视网膜神经细胞中,视网膜神经元占80％左右,其中50％以上为光感受器细胞。结论酶消化法原代培养视网膜混合神经细胞简单、可行,为视网膜神经细胞的基础研究提供良好的体外模型。     

新生儿缺氧缺血性脑病神经元特异性烯醇化酶的变化

目的研究新生儿缺血缺氧性脑病（HIE）神经元特异性烯醇化酶（NSE）的变化,探讨它们对HIE患儿病情进展、病情程度、预后判断的价值。方法符合新生儿HIE诊断标准的病例39例,分为轻度HIE组和中重度HIE组,选取同时期出生健康新生儿为对照组,采用酶联免疫法对新生儿不同时间的血清NSE浓度进行测定,并对结果进行统计学分析。结果新生儿血清NSE浓度与新生儿HIE相关,且与其严重程度正相关,组间差异具有显著性统计学意义（P〈0.05）。结论血清中NSE水平可作为判断新生儿HIE和脑损伤程度的可靠指标。     

雷公藤提取物对神经退行性疾病的作用机制研究进展

雷公藤提取物在阿尔茨海默病、帕金森病、实验性自身免疫性脑脊髓炎、脑缺血等神经退行性疾病中,通过促进B细胞淋巴瘤因子-2蛋白表达抑制神经元凋亡;通过抑制肿瘤坏死因子α、白细胞介素-1β的转录减轻神经炎症反应;通过增加多巴胺的分泌水平提高多巴胺能神经元存活率。雷公藤提取物具有显著的抗神经炎症及抗神经元凋亡作用,有望成为延缓神经退行性疾病病程的重要手段。     

Presynaptic impairment in Niemann-Pick C1-deficient neurons: not dependent on presence of glial cells

Niemann-Pick disease type C (NPC) is a progressive neurodegenerative disorder characterized by accumulation of free cholesterol in late endosomes/lysosomes. The pathological basis for the disease has been poorly understood yet. In our previous study, we have demonstrated that synaptic function is impaired in this disease. In the current study, electrophysiological and fluorescent dyes studies were used to determine whether the synaptic defects result from presynaptic or postsynaptic contributions. Furthermore, we would like to ascertain whether such defects are caused by direct effect of NPC1 deficiency in neurons or indirect effect of NPC1 deficiency in glial cells. Both mean inter-event interval of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were significantly larger in NPC1(-/-) neurons than those in the wild-type neurons, while the amplitudes and the receptor kinetics were not different compared with those in wild-type controls. Synaptic vesicle exocytosis was also slower in the NPC1(-/-) neurons. The mean time constant of destaining was larger in NPC1(-/-) neurons than in wild-type controls both in the presence and absence of glial cells. All these results indicated a general presynaptic functional impairment in the NPC1(-/-) neurons and such defects were not dependent of glial cells. Therefore, neuropathology characteristics of NPC diseases may be a more possible consequence of neuronal presynaptic dysfunction than indirect defects in glial cells.     

Reduced activation in the mirror neuron system during a virtual social cognition task in euthymic bipolar disorder

Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others' emotional expression. Relative to normal controls, BD patients showed reduced activations in the ‘mirror neuron system’, including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients.