星形胶质细胞与阿尔茨海默病

阿尔茨海默病是老年人的常见病和多发病,它的发生,发展与包括星形胶质细胞在内的多种因素有关。近年来的研究发现,星形胶质细胞在阿尔茨海默病发病的早期被激活,增生并释放多种炎症细胞因子（IL－1,IL－6,INF等）和促生长因子S100以及诱导iNOS表达,在脑内开成反复的神经免疫反应和病理改变,导致神经毒性的β－淀粉样蛋白沉积加速,神经纤维缠结形成,神经元损伤及丢失。     

老龄与年轻大鼠脑出血后星形胶质细胞反应的比较

目的 观察年龄对脑出血后星形胶质细胞反应的影响.方法 年轻(3个月龄)和老龄(16个月龄)雄性SD大鼠脑内注入100 μl自体全血,观察与年龄相关的神经胶质细胞的反应.年轻、老龄模型组大鼠分别在脑内注血后6、12、24、72 h、7、14 d时间点处死动物(每组6只)进行GFAP免疫组化.假手术组作对照.观察GFAP染色的阳性细胞表达.结果 与年轻大鼠比较,老龄大鼠脑出血后3 d星形胶质细胞的反应较弱,GFAP阳性细胞数显著低于年轻大鼠,这种状况可持续到监测14 d(P<0.01).结论 老龄大鼠脑出血应答的星形胶质细胞反应较弱,老龄是影响脑出血后脑损伤的重要因素.     

星形胶质细胞诱导维持血脑屏障特性

血脑屏障的结构、发生和诱导维持对神经系统的生理病理研究有重要意义。近年来对星形胶质细胞通过其分泌产物近距离参与对血脑屏障完整性的诱导维持的研究受到重视，对于指导临床实践具有重要作用。     

成年大鼠神经元和星形胶质细胞细胞周期蛋白依赖激酶的表达

目的 研究成年大鼠细胞周期蛋白依赖激酶（CDK）在神经元和星型胶质细胞的表达.方法 应用免疫荧光和激光扫描共聚焦显微镜观察成年大鼠生理状态下大脑皮层或海马CA1区神经元和星型胶质细胞CDK1、CDK2、CDK4的表达.结果 成年大鼠大脑皮层和海马CA1区神经元的细胞核和细胞浆均有CDK1、CDK2和CDK4表达,以胞核为主;星形胶质细胞也有CDK1、CDK2和CDK4的表达,但表达细胞数目较少,且表达这些指标的星形胶质细胞多聚集在海马CA1区.结论 成年大鼠大脑皮层和海马区的神经元和星形胶质细胞均表达CDK,而神经元的CDK表达较星形胶质细胞更为普遍.     

大鼠星形胶质细胞Toll样受体表达谱

目的探索Toll样受体4(TLR4)表达定位,揭示星形胶质细胞(AS)参与阿尔茨海默病(AD)炎症机制的可能分子机制。方法取新生1³ d的SD大鼠皮层进行星形胶质细胞的培养,传代纯化。细胞免疫荧光双标法鉴定传代后的AS及其纯度。实时PCR检测正常AS中TLRs表达谱。细胞免疫荧光双标法鉴定TLR4在AS的表达定位。结果传代培养可以纯化AS;AS表达TLR13 d的SD大鼠皮层进行星形胶质细胞的培养,传代纯化。细胞免疫荧光双标法鉴定传代后的AS及其纯度。实时PCR检测正常AS中TLRs表达谱。细胞免疫荧光双标法鉴定TLR4在AS的表达定位。结果传代培养可以纯化AS;AS表达TLR1¹1,但不同的TLRs表达量不同,其中TLR4表达水平相对较高,并且TLR4表达定位于胞膜和胞质。结论 AS参与AD炎症机制的可能分子机制。     

星形胶质细胞诱导维持血脑屏障特性

血脑屏障的结构、发生和诱导维持对这神经系统的生理病理研究有重要意义。近年来对星形胶质细胞通过其分泌产物近距离参与对血脑屏障完整性的诱导维持的研究受到重现，对于指导临床实践具有重要作用。     

自身免疫性胶质纤维酸性蛋白星形胶质细胞病研究进展

<正>胶质纤维酸性蛋白免疫球蛋白G(glial fibrillary acidic protein-IgG,GFAP-IgG)存在于多种神经免疫疾病中,例如自身免疫性脑炎(autoimmune encephalitis,AE)、多发性硬化(multiple sclerosis,MS)、视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)等。部分病毒性脑炎、化脓性脑炎、肿瘤患者也可在血清及脑脊液中检出GFAP-IgG^[1-2]。随后的一些研究发现,GFAP-IgG阳性的患者在临床中具有一定的独特性。因此,2016年Fang等[3]根据这类疾病的脑膜脑脊髓炎样表现、病程可反复发作、易合并肿瘤、     

脑缺血时星形胶质细胞与谷氨酸的相互作用

星形胶质细胞是中枢神经系统的一大类细胞 ,具有重要的生理功能。脑缺血时神经细胞外兴奋性氨基酸 ,特别是谷氨酸浓度大大增高 ,而谷氨酸的兴奋毒性在神经元死亡中起重要作用。星形胶质细胞与谷氨酸的相互作用可保护神经元 ,从而减轻缺血性脑损伤。     

星形胶质细胞与缺血性卒中

缺血性卒中时,作为“神经血管单元”的重要组成成分,星形胶质细胞可通过摄取过量兴奋性氨基酸、提供能量物质、维持胞外K+和水的平衡、清除氧自由基以及分泌神经营养因子等方式对神经元提供保护作用.文章就近年来星形胶质细胞参与缺血性卒中的机制进行了阐述.     

大鼠脊髓来源神经干细胞分化的星形胶质细胞亚型观察

目的观察大鼠脊髓来源神经干细胞分化形成星形胶质细胞的亚型。方法用悬浮培养法培养大鼠脊髓来源的神经干细胞,形成神经球后,以免疫荧光法鉴定神经干细胞;胶质纤维酸性蛋白(GFAP)抗体标记星形胶质细胞,观察其星形胶质细胞的亚型。结果神经干细胞分化第7天,观察到星形胶质细胞共有4种亚型,其中胞体延长型占2.39%±0.13%,扁平多角形占32.33%±2.01%,星形占59.88%±3.12%,双极型占5.39%±0.27%。结论大鼠脊髓来源神经干细胞分化成的星形胶质细胞具有多样性,以星形、扁平多角形为主。     

代谢型谷氨酸受体在大鼠糖尿病神经病理性疼痛中的作用

目的评价代谢型谷氨酸受体(mGluR5)在大鼠糖尿病神经病理性疼痛中的作用。方法 3月龄Wistar大鼠,雌雄不限,体重180～220g,单次腹腔注射链脲佐菌素(STZ)65mg/kg制备糖尿病大鼠神经病理性疼痛模型。模型制备成功大鼠64只,随机分为2组(n=32),糖尿病神经病理性疼痛组(D组)和mGluR5拮抗剂组(M组),另取32只正常大鼠作为对照组(C组,n=32)。M组腹腔注射mGluR5拮抗剂20mg/kg,1次/d,C、D组注射等体积生理盐水。各组分别于第2、4、6、8周(T1～4)末随机取8只大鼠,采用vonFrey纤维丝测定双后足机械缩足反应阈值(MWT),取L3～6脊髓,采用免疫组化法和RT-PCR法检测mGluR5的mRNA水平。结果与C组比较,D组T1～4时MWT降低,mGluR5mRNA水平升高(P0.05);与D组比较,M组T1～4时MWT升高mGluR5mRNA水平下降(P0.05)。结论 mGluR5激活参与大鼠糖尿病神经病理性疼痛的形成。     

Changes in sensory neuropeptides in dorsal root ganglion and spinal cord of spontaneously diabetic BB rats

This study examined the experession of the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), in the lumbar 4 and 5 dorsal root ganglion (DRG) and spinal cord of spontaneously diabetic BB rats and non-diabetic controls using quantitative immunohistochemical analysis. In both animal groups immunoreactivities for CGRP and SP were widely distributed within the neurons of DRG and in nerve fibres of the dorsal spinal cord. Image analysis of each neuropeptide subpopulation in the DRG showed that in diabetic rats the cell diameter of immunostained CGRP neurons was significantly decreased compared with controls, while no difference could be found for SP-immunoreactive (IR) neurons. The decrease in the CGRP-IR cell diameter appeared to occur mainly in medium to large neurons (30–50 m diameter; 2.2% controls, <1% diabetes), this change being parallel to an increased frequency of small-size neurons (<20 m diameter) in diabetic rats (62% controls, 69% diabetes;P<0.05). However, there was no statistical difference in the total number of cells immunostained for either CGRP or SP between control and diabetic rats. The ratio of CGRP or SP neurons compared to total cells in the ganglion was similar in control and diabetic groups. No difference could be observed for peptide immunoreactivity in the dorsal and ventral horns of either control or diabetic animals. The observed changes of perikaryal size in diabetic rats might relate to the reduced axonal calibre and conduction velocity observed in these animals, and indicate that subpopulations of sensory neurons are affected differently by diabetes.     

Nocturnal neuropathic pain in diabetic patients may be caused by spinal stenosis.

BACKGROUND: Nocturnal exacerbation of neuropathic symptoms (NENS) is a recognized symptom of diabetic peripheral neuropathy (DPN). Symptoms are often worse in bed, may not be controlled with medication and disrupt sleep patterns. NENS can also be present in patients with spinal stenosis (SS), with or without concomitant peripheral neuropathy and may be related to sleep position. Extension position of the spine decreases the diameter of both the central canal and lateral recesses, which may compress or otherwise affect nerves controlling sensation from the feet and legs. Altering sleep position can reduce or eliminate symptoms. Modifications include sleeping in a recliner, with a pillow underneath the thighs if sleeping on the back, between the thighs if sleeping on the side, or under the stomach transversely if sleeping on the stomach. In addition, reducing nerve compression during the day by full-time use of a wheeled walker set to induce lumbosacral flexion may reduce NENS. METHODS AND RESULTS: Retrospective patient review identified patients presenting with DPN including NENS, who noted alteration of NENS by changing body position, who also had walking and standing limitations consistent with SS. They underwent 'positional testing', involving modification of sleep position, and full-time 3-day use of a rollator walker, which may reduce symptoms of SS. Most reported good or excellent improvement of NENS. CONCLUSIONS: NENS, especially if affected by body position, or if accompanying a pattern of walking limitation improved with wheeled support, should lead to suspicion of SS. Positional testing should be considered in possible cases. Clinical use and further investigation are indicated.     

重复经颅磁刺激联合加巴喷丁治疗脊髓损伤后神经病理性疼痛的临床观察

目的探讨重复经颅磁刺激（rTMS）联合加巴喷丁治疗脊髓损伤（SCI）后神经病理性疼痛（NP）的临床疗效。 方法纳入苏州瑞盛康复医院神经康复科自2017年1月至2018年12月收治的60例SCI后NP患者,用随机数字表法分为观察组与对照组,每组30例。2组患者均口服加巴喷丁,观察组给予M1区10 Hz的rTMS治疗,对照组给予M1区相同模式、相同音量的声音假刺激,在治疗前和治疗后第1、2、4、6周分别采用视觉模拟评分法（VAS）对疼痛进行评定,治疗前、后采用汉密顿抑郁量表（HAMD）及焦虑量表（HAMA）分别对抑郁程度和焦虑程度评定,同时观察加巴喷丁最大用量和不良反应及TMS治疗不良事件。 结果治疗后第1周,2组患者的VAS评分较治疗前均无明显改善差异无统计学意义（P>0.05）,2组患者的VAS评分比较,比较差异无统计学意义（P>0.05）;治疗后第2、4、6周,观察组患者的VAS评分均低于对照组,第6周差异更为显著,差异具有统计学意义（P<0.05）。治疗6周后,观察组患者的HAMD评分和HAMA评分优于对照组,差异具有统计学意义（P<0.05）。 结论加巴喷丁联合rTMS治疗SCI后NP具有较好的临床疗效,能够有效控制疼痛,改善SCI患者的抑郁、焦虑情绪状态以及因疼痛导致的睡眠障碍,具有较好的安全性、可靠性。     

Small‐fibre involvement in diabetic patients with neuropathic foot pain

Aims To assess small‐fibre involvement in diabetic patients with neuropathic pain. Methods Peripheral nerve function was assessed in 30 patients with Type 2 diabetes mellitus (T2DM, n = 24) or impaired glucose tolerance (IGT, n = 6), and clinical symptoms of neuropathic pain in the feet, using nerve conduction studies, autonomic tests, thermal quantitative sensory testing (T‐QST) and quantification of intra‐ and subepidermal nerve fibre densities in skin punch biopsies. Results Clinical signs of isolated small‐fibre sensory involvement were present in 13 patients [pure small‐fibre neuropathy (pSFN)], seven patients had isolated positive sensory symptoms without neurological deficits (pSFN–). Ten patients had concomitant electrophysiological and/or clinical signs of large‐fibre sensory involvement [mixed‐fibre neuropathy (MFN)]. Twenty‐seven patients (90%) had both reduced skin innervation and abnormalities of the T‐QST parameters. Two other patients displayed either abnormal skin innervation or T‐QST, and only one patient had normal findings on both tests. The criteria of small‐fibre neuropathy (SFN) were met in all 20 patients without large‐fibre involvement. Small‐fibre involvement was also present in the 10 MFN patients. Both T‐QST and skin biopsy parameters revealed significant differences between these clinical subgroups, with increased severity of small‐fibre involvement in the MFN group. Autonomic dysfunction was found in 43% of patients and did not correlate with either clinical, T‐QST or skin biopsy data. Conclusions Although the exact mechanism of neuropathic pain in diabetic patients is not known, pain is almost invariably accompanied by small‐fibre dysfunction and pathology irrespective of autonomic or large‐fibre involvement.     

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain.     

Effect of gbpapentin on the expression of Nrf2 in dorsal root ganglion neurons of diabetic neuropathic pain rats

<正>Objective To investigate the effect of systemic administration of gabapentin on the expression of Nrf2 in dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP). Methods 60 male SD rats weighing 200-220 g were randomly divided into 4groups (n=15 each):control group (group C),DNP