Smooth muscle hypertrophy in distal airways of sensitized infant rhesus monkeys exposed to house dust mite allergen

BACKGROUND: Airway smooth muscle hypertrophy is closely associated with the pathophysiology of hyper-reactive airways in allergic asthma. OBJECTIVE: To determine whether repeated exposure to allergens during postnatal lung development promotes remodelling of airway smooth muscle. METHODS: Infant, male rhesus monkeys (30-day-old) were sensitized to house dust mite allergen (HDMA) and then exposed to HDMA aerosol periodically over 5 months. Smooth muscle mass and bundle size and abundance in conducting airways were measured and compared with age-matched control (filtered air-exposed) monkeys. RESULTS: Total smooth muscle mass and average bundle size were significantly greater in the conducting airways of monkeys exposed to HDMA. Smooth muscle bundle abundance was not affected by exposure to HDMA. CONCLUSION: Repeated cycles of allergen exposure alter postnatal morphogenesis of smooth muscle, affecting both total mass and bundle size, in conducting airways of infant monkeys.     

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

It is currently widely accepted that immune activation in HIV-infected individuals leads to a severe loss of CD4⁺ T cells and the progression to AIDS. However, the underlying mechanism of this immune activation remains unclear. Experimental data suggest that the activation of plasmacytoid dendritic cells (pDCs) by plasma viremia may play a critical role in HIV-induced immune activation. In this study, we found that the level of immune activation was higher in the late phase of SIVmac239 infection compared with chronic infection, which suggests that immune activation might be related to disease progression in SIVmac239-infected non-human primate models. Our work also showed that chloroquine could effectively inhibit the activation of pDCs in vitro and in vivo. However, chloroquine treatment of SIVmac239-infected macaques had no significant influence on the Cellular composition of peripheral blood in these animals.     

Neural correlate of spatial (mis‐)localization during smooth eye movements

The dependence of neuronal discharge on the position of the eyes in the orbit is a functional characteristic of many visual cortical areas of the macaque. It has been suggested that these eye‐position signals provide relevant information for a coordinate transformation of visual signals into a non‐eye‐centered frame of reference. This transformation could be an integral part for achieving visual perceptual stability across eye movements. Previous studies demonstrated close to veridical eye‐position decoding during stable fixation as well as characteristic erroneous decoding across saccadic eye‐movements. Here we aimed to decode eye position during smooth pursuit. We recorded neural activity in macaque area VIP during steady fixation, saccades and smooth‐pursuit and investigated the temporal and spatial accuracy of eye position as decoded from the neuronal discharges. Confirming previous results, the activity of the majority of neurons depended linearly on horizontal and vertical eye position. The application of a previously introduced computational approach (isofrequency decoding) allowed eye position decoding with considerable accuracy during steady fixation. We applied the same decoder on the activity of the same neurons during smooth‐pursuit. On average, the decoded signal was leading the current eye position. A model combining this constant lead of the decoded eye position with a previously described attentional bias ahead of the pursuit target describes the asymmetric mislocalization pattern for briefly flashed stimuli during smooth pursuit eye movements as found in human behavioral studies.     

风疹病毒减毒活疫苗猴体神经毒力试验

目的 评价风疹病毒减毒活疫苗的潜在神经毒力。方法 普通级恒河猴随机分为2组,风疹病毒减毒活疫苗组10只,对照组2只,采用猴脑定位的方法将风疹病毒减毒活疫苗接种于猴两侧丘脑,对照组接种等体积生理盐水;检测血清抗体效价;并观察动物是否产生抽搐、癫痫、共济失调、震颤等神经毒力症状,以及风疹病毒减毒活疫苗对一般体征、饮食、体温的影响;风疹病毒减毒活疫苗组疫苗接种后20 d、对照组接种后31 d进行脑部及脊髓大体解剖和组织病理学检查,以评价该疫苗的神经毒力。结果 猴丘脑注射疫苗后,风疹病毒减毒活疫苗组动物血清抗体效价呈阳性,免疫应答较好,对照组均呈阴性;动物未出现情绪激怒、呕吐、颈强直、抽风惊厥等神经毒力症状;动物外观、行为活动、饮食情况、体温等各方面均未见明显异常;组织病理学检查未见药物引起脑及脊髓的明显病理学改变。结论 风疹病毒减毒活疫苗在猴体中不具有神经毒力。     

Directional asymmetry in vertical smooth-pursuit and cancellation of the vertical vestibulo-ocular reflex in juvenile monkeys

Young primates exhibit asymmetric eye movements during vertical smooth-pursuit across a textured background such that upward pursuit has low velocity and requires many catch-up saccades. The asymmetric eye movements cannot be explained by the un-suppressed optokinetic reflex resulting from background visual motion across the retina during pursuit, suggesting that the asymmetry reflects most probably, a low gain in upward eye commands (Kasahara et al. in Exp Brain Res 171:306–321, 2006). In this study, we examined (1) whether there are intrinsic differences in the upward and downward pursuit capabilities and (2) how the difficulty in upward pursuit is correlated with the ability of vertical VOR cancellation. Three juvenile macaques that had initially been trained only for horizontal (but not vertical) pursuit were trained for sinusoidal pursuit in the absence of a textured background. In 2 of the 3 macaques, there was a clear asymmetry between upward and downward pursuit gains and in the time course of initial gain increase. In the third macaque, downward pursuit gain was also low. It did not show consistent asymmetry during the initial 2 weeks of training. However, it also exhibited a significant asymmetry after 4 months of training, similar to the other two monkeys. After 6 months of training, these two monkeys (but not the third) still exhibited asymmetry. As target frequency increased in these two monkeys, mean upward eye velocity saturated at ∼15°/s, whereas horizontal and downward eye velocity increased up to ∼40°/s. During cancellation of the VOR induced by upward whole body rotation, downward eye velocity of the residual VOR increased as the stimulus frequency increased. Gain of the residual VOR during upward rotation was significantly higher than that during horizontal and downward rotation. The time course of residual VOR induced by vertical whole body step-rotation during VOR cancellation was predicted by addition of eye velocity during pursuit and VOR x1. These results support our view that the directional asymmetry reflects the difference in the organization of the cerebellar floccular region for upward and downward directions and the preeminent role of pursuit in VOR cancellation.     

慢性炎症在X射线诱发恒河猴卵巢组织持续损伤中的潜在作用

目的:探讨在X射线诱发恒河猴卵巢损伤中慢性炎症是否发挥重要作用。方法:14只月经周期规律的成年雌性恒河猴（8～14岁）,随机分为3组（3只/组）:假照射（Sham）组（n=8）、卵巢照射（OXI） 组（n=3）、X射线照射+FTY-720（免疫抑制剂）（FTY-720）组（n=3）。Sham组给与溶剂PET+假手术（保留卵巢血管蒂,将卵巢移出腹腔）,OXI组动物卵巢移出腹腔后给与15 Gy X射线照射,FTY-720组卵巢内行0.2 mmol/L FTY-720灌注1周后给与15 Gy X射线照射。各组手术操作相同,结束后将卵巢复位,均于早卵泡期行卵巢组织取材[照射结束后第（316±7）天]。免疫组织化学染色法检测卵巢组织单核细胞趋化蛋白-1（MCP-1）、CD11b和CD68的表达并计数CD11b、CD68阳性细胞,ELISA法检测照射结束后第３个月和第９个月血清MCP-1、白细胞介素（IL）-6水平。结果:OXI组卵巢组织MCP-1阳性染色强于Sham组和FTY-720组,而FTY-720组MCP-1表达与Sham组表达情况相似。与Sham组相比,OXI组CD11b阳性细胞数量明显增多（P<0.05）;而FTY-720组CD11b阳性细胞数量明显少于OXI组（P<0.05）,且其与Sham组相比较,差异无统计学意义（P>0.05）。3组间CD68阳性细胞数量差异无统计学意义（P>0.05）,但观察到OXI组卵巢组织CD68阳性细胞数量呈增高趋势,而FTY-720组变化不明显,接近Sham组水平。照射后第３个月,3组间血清MCP-1浓度差异不显著（P >0.05）;第９个月时,OXI组MCP-1浓度明显高于Sham组（P=0.031 4）,而FTY-720组明显低于OXI组（P=0.017 2）。血清IL-6仅在OXI组中检测到,照射后第３个月时为（4±1） pg/mL,９个月时为（9±6） pg/mL（P >0.05）。结论:X射线照射可诱发卵巢慢性炎症,而FTY-720能够抑制该炎症,降低恒河猴卵巢组织内MCP-1的表达、CD11b+和CD68+巨噬细胞的浸润,减少血清MCP-1、IL-6含量。     

高+Gx对猴肝细胞c-fos表达的影响

目的:观察航天应急返回过程中高正加速度( Gx)对肝脏细胞c-fos基因表达的影响．方法:选用♂猕猴(共9只)为对象,随机分为4组,对照组承受 1Gx,300 s的超重作用;实验组根据承受过载峰值的大小分为3个亚组,其承受过载峰值分别为 15Gx,200 s; 18Gx, 165 s; 21Gx,140 s．观察高 Gx对猴肝脏细胞c-fos基因表达的影响．结果:实验组肝脏细胞胞质呈现不同程度的水肿及泡状变性,c-fos基因表达明显增强,呈弥漫性细胞质内棕黄色着色;肝细胞c-fos基因表达程度随超重剂量的增加有增强趋势．对照组肝脏组织病理学改变程度明显较实验组轻微,c-fos基因表达亦明显减弱．结论: Gx可引起猴肝脏组织细胞c-fos基因表达增强,提示有早期肝脏组织损伤．     

MRI导引下壳核靶向注射GDNF治疗帕金森病的实验研究

目的 探讨MRI导引下壳核置管注射神经胶质细胞源性神经生长因子(GDNF)治疗帕金森病(PD)的实验价值.方法 PD猴动物模型3只,在无菌条件下,采用MRI引导立体定向技术,在PD猴模型右侧壳核置管输注GDNF.结果所有实验动物置管术后反应良好,在6周的给药期间无不良反应,PD症状明显改善.结论 MRI导引下壳核置管输注GDNF治疗PD猴模型安全、有效.     

Cross‐sectional and longitudinal reproducibility of rhesus macaque brain metabolites: A proton MR spectroscopy study at 3 T

Non‐human primates are often used as preclinical model systems for (mostly diffuse or multi‐focal) neurological disorders and their experimental treatment. Due to cost considerations, such studies frequently utilize non‐destructive imaging modalities, MRI and proton MR spectroscopy (¹H MRS). Cost may explain why the inter‐ and intra‐animal reproducibility of the ¹H MRS observed brain metabolites, are not reported. To this end, we performed test‐retest three‐dimensional brain ¹H MRS in five healthy rhesus macaques at 3 T. Spectra were acquired from 224 isotropic (0.5 cm)³ = 125 μL voxels, over 28 cm³ (～35%) of the brain, then individually phased, frequency aligned and summed into a spectrum representative of the entire volume of interest. This dramatically increases the metabolites' signal‐to‐noise ratios, while maintaining the (narrow) voxel linewidth. The results show that the average N‐acetylaspartate, creatine, choline, and myo‐inositol concentrations in the macaque brain are: 7.7 ± 0.5, 7.0 ± 0.5, 1.2 ± 0.1 and 4.0 ± 0.6 mM/g wet weight (mean ± standard deviation). Their inter‐animal coefficients of variation (CV) are 4%, 4%, 6%, and 15%; and the longitudinal (intra‐animal) CVs are lower still: 4%, 5%, 5%, and 4%, much better than the 22%, 33%, 36%, and 45% intra‐voxel CVs, demonstrating the advantage of the approach and its utility for preclinical studies of diffuse neurological diseases in rhesus macaques. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.