Parathyroid hormone-related protein is expressed by transformed and fetal human astrocytes and inhibits cell proliferation

Parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP receptor are expressed in most normal tissues, including brain, where PTHrP is though to act locally in an autocrine or paracrine fashion. Previous in situ localization studies in adult rodents have documented CNS PTHrP expression in neurons but not in glial cells. However, a recent report describing immunoreactive PTHrP in human astrocytomas suggests that PTHrP expression may be a marker of dedifferentiation and/or malignant transformation in glial cells. To begin to test this hypothesis, constitutive and regulated PTHrP expression were examined in cultured fetal and transformed (U-373 MG) human astrocytes. PTHrP was expressed in untreated fetal astrocytes and U-373 MG cells, as determined by Northern analysis, immunocytochemical staining, and detection of PTHrP(1-84) protein in conditioned media. Epidermal growth factor and tumor necrosis factor, important growth factors in astrocyte development and malignant transformation, stimulated PTHrP expression in both cell types. Treatment of U-373 MG cells or fetal astrocytes with PTHrP(1-34) consistently inhibited cellular proliferation, as measured by [(3)H]-thymidine incorporation. These findings suggest that PTHrP, a peptide whose expression is induced by mitogens in both immature and transformed human astrocytes, may feedback inhibit cellular proliferation, an effect that may be of importance during malignant transformation as well as CNS development. Furthermore, when combined with previous evidence of PTHrP expression by PTH/PTHrP receptor-positive neurons, our demonstration of regulated PTHrP expression by receptor-positive astrocytes identifies PTHrP as a potential peptide mediator of cross-talk between glial cells and neurons.     

Co-induction of HSP70 and heme oxygenase-1 in macrophages and glia after spinal cord contusion in the rat

HSP70 and heme oxygenase-1 (HO-1) are thought to be markers of cell injury and oxidative stress, respectively. We have immunolocalized these proteins in the spinal cord at 1-14 days after contusion. HSP70 and HO-1 were co-induced in glia and macrophages within the injured segment at all time points. This co-induction may reflect complementary functions that serve to protect these cells as they respond to the postcontusional environment.     

高热对星形胶质细胞GFAP表达的影响

目的　研究高热对大脑星形胶质细胞中胶质原纤维酸性蛋白 (glialfibrillaryacidicprotein ,GFAP)表达的影响及后果。方法　分离培养脑星形胶质细胞 ;42℃分别作用细胞 1、2、4h后 ,进行免疫学染色 ,观察GFAP表达的变化 ;采用改良Lowry法测定星形胶质细胞条件培养液中总蛋白含量。结果　在高温条件下 ,脑星形胶质细胞反应性增生。 42℃作用 4h后 ,GFAP表达显著减少 ,细胞条件培养液中总蛋白含量减少 2 6μg/ml(由 3 83 μg/ml降低到 3 5 7μg/ml)。 结论　高热条件可以下调脑星形胶质细胞GFAP的表达 ,影响星形胶质细胞生物学功能 ,在中枢损伤的发生发展过程中发挥作用     

人视网膜星形胶质细胞发育及起源的研究

背景 视网膜星形胶质细胞是视网膜主要的神经胶质细胞,其起源及演变过程一直是国内外研究的热点和难点. 目的 探讨人胚胎眼视网膜星形胶质细胞的起源及发育.方法 收集33例自愿终止妊娠的流产人胚胎眼标本,其中8 ～12孕周者20例,15～ 17孕周者2例,19～ 23孕周者4例,25～ 28孕周者4例,30 ～32孕周者3例.对眼球壁切片进行常规组织病理学检查以观察不同胚龄人视网膜发育的形态学变化,分别采用免疫组织化学法及免疫荧光法动态观察不同胚龄人视网膜星形胶质细胞起源位点及发育过程中胶质纤维酸性蛋白( GFAP)表达的变化.结果 人胚6～7周视杯处于视网膜分层发育阶段,9周时视杯内层原无细胞层出现分化不成熟的圆短梭形细胞；胚龄15周时视网膜主要层次可见,分化的细胞增加,但未发现GFAP阳性细胞；胚龄19周视网膜可见梭形细胞从返折部原始神经上皮迁出,并可见这些细胞中GFAP呈阳性表达；胚龄25～ 26周后极部视网膜可见GFAP表达阳性的梭形细胞,这些细胞围绕视网膜血管分布,与血管壁联系密切,邻近锯齿缘处的视网膜内层可见表达GFAP的星形或梭形细胞与睫状体非色素上皮相连,但锯齿缘稍后与赤道区之间并未见GFAP阳性细胞；胚龄28周,视网膜星形胶质细胞呈典型的星状,其突起伸达视网膜内网状层. 结论 人视网膜星形胶质细胞至少存在3个起源位点,即血管前体细胞/周皮细胞、视盘旁原始神经上皮及邻近锯齿缘的睫状体无色素上皮.     

Infiltrated regulatory T cells and Th2 cells in the brain contribute to attenuation of sepsis-associated encephalopathy and alleviation of mental impairments in mice with polymicrobial sepsis

Sepsis-associated encephalopathy (SAE) increases not only morbidity and mortality but has been associated with long-lasting mental impairment after hospital discharge in septic patients. Recently, studies have shown that these mental impairments are caused by infection-induced neuroinflammation. However, the role of T cells in the pathogenesis of SAE and mental impairments remains unclear. Thus, in this study, we aimed to clarify how immune cells, especially T cells, influence the development and recovery of these disorders. In the cecal slurry (CS)-induced septic mouse model, we performed three different kinds of behavioral tests, open-field test, marble burying test, and forced swimming test, and observed anxiety-like behavior in septic mice. Additionally, increased interleukin (IL)-1β and IL-6 expression levels, and infiltration of neutrophils and T cells were examined in the brain of septic mice, 10 days after sepsis onset. Twenty days after sepsis onset, the septic mice could recover the number of astrocytes. At day 30, expression levels of IL-1β and tumor necrosis factor (TNF)-α returned to normal levels in the cerebral cortex of septic mice. Interestingly, resolution of neuroinflammation and alleviation of depression were delayed in septic mice treated with FTY720, which inhibits sphingosine-1-phosphate (S1P)-dependent lymphocyte egress from lymph nodes. On analyzing the brain T cells with or without FTY720 in septic mice, the FTY720 untreated mice presented increased regulatory T cells (Treg) and Th2 cells in the brain, whereas the FTY720 treated mice demonstrated increased Th17 in the brain at day 30. Furthermore, in FTY720 treated septic mice, the number of astrocytes in the cerebral cortex remained reduced at day 30. These results suggest that infiltrated Treg and Th2 cells contribute to the attenuation SAE and alleviate SAE-induce mental disorder by resolving neuroinflammation in the chronic phase of sepsis.     

S100B蛋白与小儿七氟烷麻醉躁动的相关性研究

目的 探讨星形胶质细胞标志物S100B蛋白浓度变化与七氟烷麻醉躁动中的相关性.方法 选择在全麻下行择期白内障手术的患儿30例,美国麻醉医师协会麻醉风险评分(ASA)Ⅰ或Ⅱ级,年龄3～6岁.吸入麻醉诱导为8％七氟烷,待患儿睫毛反射消失后插入喉罩.术中采用3.0％～3.5％的七氟烷维持,调节氧流量2～3 L/min,保持患儿自主呼吸.术毕停止吸入七氟烷,拔除喉罩,记录躁动发生情况.分别于吸入七氟烷前,吸入七氟烷后15 min和术后10 min 3个时间点采集外周静脉血2～3 ml,静置离心后,检测血清S100B蛋白的浓度.结果 30例患儿术前、术中和术后血清S100B蛋白平均浓度分别为(62.76±32.51)、(47.90±22.20)、(48.05±23.53)ng/L,术中和术后浓度值较术前明显降低(P＜0.01),但术中和术后二者浓度值的差异无统计学意义(P＞0.05).其中,躁动患儿术中和术后平均血清S100B蛋白浓度均较术前明显下降[(49.71±25.20) ng/L vs.(68.26±39.40) ng/L,(55.59±30.54)ng/L vs.(68.26±39.40)ng/L,P均＜0.01],术中和术后的差异无统计学意义(P＞0.05);未发生躁动患儿术中和术后平均血清S100B蛋白浓度均较术前明显降低[(46.71±20.64)ng/Lvs.(59.1 1±27.62)ng/L,(43.18±16.95)ng/L vs.(59.11±27.62)ng/L,P均＜0.01],术中和术后的差异无统计学意义(P＞0.05).躁动患儿术前、术后S100B蛋白浓度差值与与躁动评分无相关性(r=0.045,P＞0.05).结论 S100B蛋白浓度在麻醉恢复期患儿躁动发生时明显下降,星形胶质细胞并未在躁动过程中表达增强,S100B蛋白浓度的变化与躁动的严重程度无相关性.     

组织内AEG-1表达情况对葡萄膜黑色素瘤病理特征的影响

目的 探究组织内星形胶质细胞活化基因-1(AEG-1)表达情况对葡萄膜恶性黑色素瘤(UM)病理特征的影响。方法 选取2016年3月～2018年8月我院眼科诊治的62例(62眼)于病理室存放的UM石蜡组织标本纳入研究组。并选取同期20例(20眼)因外部原因受伤采取眼球摘除术但少量UM或绝大部分葡萄膜组织正常的石蜡组织标本作为对照组。对比分析两组患者AEG-1基因表达情况以及AEG-1表达情况与UM病理特征的相关性。结果 UM组织中AEG-1 mRNA相对表达量为(1.09±0.05),正常葡萄膜膜组织中AEG-1 mRNA相对表达量为(1.01±0.12),差异有统计学意义(P0.05);研究组62例(62眼)AEG-1阳性表达为37眼(59.68%),阴性表达为25眼(40.32%);对照组20例(20眼)AEG-1均呈阴性表达,差异有统计学意义(P0.05);肿瘤高度8 mm、累及睫状体、侵犯巩膜导管、眼外生长、视盘受累以及继发视网膜脱落与AEG-1高表达均有明显相关性(P0.05)。结论 UM高度8 mm、累及睫状体、侵犯巩膜导管、眼外生长、继发视网膜脱落及视盘受累病理特征均与AEG-1的高表达具有密切联系,显著影响UM转移风险和预后,为UM临床诊断和治疗提供有效参考。