双侧坐骨神经及股神经离断并固定大鼠神经肽Y水平对骨密度的影响

背景：以往研究认为,刺激坐骨神经及中枢神经受伤可使神经肽Y含量发生改变,神经肽Y对破骨细胞产生作用,影响骨代谢。 目的：验证双侧坐骨神经、股神经失神经及固定后神经肽物质对大鼠双侧胫骨骨密度的影响,并进行相关性分析。 设计、时间及地点：随机对照动物实验,于2006-09/11在湘南学院附属医院完成。 材料：10周龄SD雄性大鼠96只,体质量220~250 g,用于制备失神经支配模型。 方法：96只SD大鼠按数字表法随机分为3组,每组32只。①失神经支配组：切断大鼠两侧后肢坐骨神经和两侧股神经,远端游离5 mm,缝合切口。②固定组：大鼠切断神经,程序同前,继之采用管型石膏固定。③对照组：行假手术,仅暴露神经,然后缝合伤口。 主要观察指标：实验期间大鼠的一般情况。造模后1,10,30,60 d每组分别处死大鼠8只,观察双侧胫骨骨密度和神经肽Y的变化及神经肽Y水平与骨密度水平的相关性。 结果：96只SD大鼠均进入结果分析。①失神经后神经肽Y含量先降低,后升高,随着失神经支配时间的延长,神经肽Y持续升高,超过正常水平。②固定组神经肽Y含量先升高,后下降,但随着固定时间的延长,逐步升高并超过正常水平。③随着神经肽Y含量变化,大鼠双侧胫骨骨量也相应发生改变,大鼠失神经、固定30 d后双侧胫骨骨密度明显下降。失神经及固定后神经肽Y与骨密度含量变化高度相关(P < 0.01)。 结论：失神经支配及固定后大鼠神经肽Y含量变化均与骨密度改变具有高度相关,故可认为神经肽Y可作为骨质疏松形成的关键指标之一。     

降钙素基因相关肽神经生长因子与失神经支配兔骨折愈合

背景：骨折不愈合严重影响患者生活质量,神经生长因子用于骨不连的防治是重建外科领域研究的重点和方向。 目的：观察神经生长因子降钙素基因相关肽对失神经支配兔骨折愈合的影响。 方法：构建大白兔失神经支配腓骨骨折模型后,实验组骨折端局部注射降钙素基因相关肽10 μg,每2 d一次;对照组骨折端局部注射等量生理盐水。术后2,4,6周分别测定静脉血中肾上腺素和去甲肾上腺素的水平,并进行生物力学和组织学分析。 结果与结论：术后两组血清肾上腺素和去甲肾上腺素水平均有显著增高,在术后第4周达到最高峰,比术前高出1倍以上,第6周时出现下降,但仍然显著高于术前;术后2,4,6周,实验组肾上腺素和去甲肾上腺素血清水平较对照组显著增高,差异具有显著性意义(P < 0.05~0.01)。在三点弯曲实验中,实验组骨痂的抗弯强度明显高于对照组(P < 0.05~0.001);术后第6周时苏木精-伊红染色可见实验组骨痂中的透明软骨细胞已被成骨细胞替代,对照组骨痂中的软骨细胞仍没有完全成骨细胞化。提示神经生长因子降钙素基因相关肽对失神经支配兔骨折愈合具有明显的促进作用。 关键词：神经生长因子;降钙素基因相关肽;骨折愈合;生物力学;生物化学     

失神经骨骼肌萎缩与氯沙坦通过核因子κB/MuRF1通路的延缓作用

背景：在失神经骨骼肌萎缩中,核因子κB /MuRF1通路是最关键的分子机制之一,抑制该通路可以提高失神经骨骼肌的力量,保持肌肉数量和促进肌肉再生。 目的：探讨核因子κB、MuRF1在失神经骨骼肌中的表达及氯沙坦对核因子κB/MuRF1通路的影响作用,以期寻找延缓失神经骨骼肌萎缩的新途径。 方法：将Wista大鼠随机分为3组：失神经对照组、氯沙坦治疗组建立右下肢失神经腓肠肌动物模型。氯沙坦治疗组大鼠采用氯沙坦以10 mg/(kg•d)空腹灌胃;失神经对照组大鼠以等剂量生理盐水灌胃,以不做处理的大鼠为正常对照。采用RT-PCR和Western Blotting 检测术后2,14,28 d时大鼠腓肠肌核因子κB和MuRF1的mRNA和蛋白表达水平,并结合肌肉失质量比分析其相关性。 结果与结论：大鼠腓肠肌失神经支配后核因子κB和MuRF1的mRNA和蛋白表达在2,14,28 d持续增加(P < 0.05),而且二因子的表达线性相关有显著性意义(P < 0.05)。失神经支配后14,8 d氯沙坦治疗组腓肠肌湿质量比高于同期失神经对照组(P < 0.05),氯沙坦治疗组两因子mRNA和蛋白的表达在各个时间点低于失神经对照组(P < 0.05)。核因子κB、MuRF1在失神经肌萎缩中表达增高,而且是同一通路。结果提示氯沙坦可以通过干扰核因子κB、MuRF1mRNA和蛋白质的表达来延缓失神经骨骼肌萎缩。     

成肌调节因子Myf-5在失神经骨骼肌萎缩不同时段的表达

背景：成肌调节因子Myf-5是参与肌肉发生过程分子调控、启动和维持骨骼肌细胞生长发育的重要基因,可能与失神经骨骼肌萎缩的发生有关。 目的：观察不同部位、不同时段骨骼肌失神经支配后成肌调节因子Myf-5基因的表达情况。 设计、时间及地点：随机对照动物实验,于2008-03/04在山西医科大学完成。 材料：选择健康8周龄雄性SD大鼠24只,随机分成4组,即假手术组(有神经支配)、去神经2 d组、去神经7 d组、去神经28 d组,每组6只。 方法：假手术组不切断坐骨神经,仅做假手术。去神经组右下肢后部中段切断坐骨神经1 cm以上,分别于去神经第2,7,28天用脊椎脱臼法处死大鼠,分离出右小腿的胫骨前肌、比目鱼肌、腓肠肌、跖肌标本。 主要观察指标：用反转录-聚合酶链反应技术检测各组肌肉Myf5 mRNA表达情况,抗Myf-5 多克隆抗体免疫组织化学染色(ABC 法),测量灰度值。 结果：去神经骨骼肌早期,Myf-5的mRNA在去神经支配后第2,7,28天均表达上调(P < 0.05)。Myf-5 抗体阳性染色细胞核数在SD大鼠骨骼肌失神经28 d时的肌卫星细胞中最多。 结论：Myf-5在大鼠失神经骨骼肌萎缩早期不同肌肉表达均为上调。大鼠骨骼肌失神经支配后早期肌卫星细胞中Myf-5表达上调。     

骨折愈合过程中降钙素基因相关肽表达与脑损伤的影响

背景：临床观察及实验研究发现合并中枢神经损伤的骨折愈合加速,但其具体机制尚未明确。 目的：观察股骨骨折合并脑损伤大鼠骨痂中降钙素基因相关肽及其mRNA的表达变化,探讨脑损伤对骨折愈合的影响及作用机制。 设计、时间及地点：随机对照动物实验,于2007-01/10在华北煤炭医学院骨科实验室完成。 材料：健康12周龄雌性SD大鼠64只,建立大鼠开放骨折模型。 方法：骨折造模后64只SD大鼠随机数字法分为骨折合并脑损伤组和单纯骨折组,每组32只,骨折合并脑损伤组接着制备脑损伤模型。造模后7,14,21,28 d分批麻醉并处死动物,苏木精-伊红染色观察骨折愈合情况,免疫组织化学染色及原位杂交检测降钙素基因相关肽及其mRNA的表达变化。 主要观察指标：①造模后28 d大鼠右侧股骨X射线平片表现。②造模后不同时间点两组大鼠骨痂苏木精-伊红染色、免疫组织化学染色及原位杂交结果。 结果：64只SD大鼠均进入结果分析。①X射线平片显示与单纯骨折组相比,骨折合并脑损伤组骨折端骨痂形成早,骨痂量多。②苏木精-伊红染色示单纯骨折组呈典型骨折愈合过程,而骨折合并脑损伤组骨痂形成及改造提前,骨折愈合加速。免疫组织化学染色显示骨折愈合过程中内皮细胞、骨祖细胞、软骨细胞及成骨细胞表达降钙素基因相关肽。骨折合并脑损伤组造模后各时间点阳性细胞数均高于单纯骨折组,差异有显著性意义(P < 0.05)。原位杂交检测示骨折合并脑损伤组造模后7,14,21 d表达降钙素基因相关肽mRNA的成骨细胞数均高于单纯骨折组,差异有显著性意义(P < 0.05)。 结论：脑损伤对骨折愈合有促进作用,可能与合并脑损伤后降钙素基因相关肽及其mRNA表达水平升高有关。     

大鼠松质骨中降钙素基因相关肽在脊髓损伤后的变化

背景：细胞因子异常及神经功能的异常、激素水平的改变均参与了脊髓损伤后骨质疏松的发生，以往对细胞因子及激素改变的研究较多，而对神经异常对骨调节的研究相对较少。 目的：课题创新性地应用血生化与免疫组织化学相结合的方法，观察脊髓损伤后大鼠松质骨中神经多肽降钙素基因相关肽的变化，分析其在脊髓损伤后骨质疏松中的意义。 设计、时间及地点：随机对照动物实验，于2008-09/12在解放军第四军医大学骨科研究所实验室完成。 材料：3月龄SD大鼠48只，体质量为(210±16) g，随机均分为脊髓损伤组与对照组，每组24只。 方法：脊髓损伤组于T10处完全横断脊髓；对照组仅行椎板切除术。 主要观察指标：术后1，3，6 周分批每组随机取8只动物处死。测定血骨特异性碱性磷酸酶、Ⅰ型胶原氨基末端肽；对股骨髁松质骨行降钙素基因相关肽免疫组织化学染色,结合计算机图像分析系统对降钙素基因相关肽免疫阳性神经的染色强度进行定量分析。 结果：脊髓损伤组各时间段血清Ⅰ型胶原氨基末端肽浓度显著高于对照组(P < 0.05或0.01)，各时间段血清骨特异性碱性磷酸酶活性低于对照组，但差异无显著性意义(P > 0.05)。对照组各时间段分布于小梁骨内的降钙素基因相关肽免疫阳性神经呈强阳性，脊髓损伤组降钙素基因相关肽较对照组减弱( P < 0.05或0.01)。 结论：脊髓损伤后松质骨内降钙素基因相关肽的减弱可能与脊髓损伤后骨质疏松的发生有关。     

烫伤创面愈合后的瘢痕形成与神经支配*★

背景：既往研究表明神经因素在创面愈合中具有重要调控作用，但有关神经调节与创面愈合后瘢痕形成之间的关系鲜有报道。 目的：观察烧伤创面愈合过程中神经支配与创面愈合质量之间的关系。 方法：将30只大鼠右侧T9~L1阶段脊神经根切断，制作失神经支配皮肤模型；然后在大鼠背部右侧失神经支配皮肤区域制作直径4 cm的深Ⅱ度烫伤创面，设为模型组，左侧对称正常皮肤制作同样的创面，设为对照组，伤后连续观察创面变化，于7，14，21 d采用免疫组织化学法观察Ⅰ和Ⅲ胶原分泌情况，并计算Ⅰ/Ⅲ型胶原比例的变化，探讨创面愈合速度及愈合质量。 结果与结论：模型组Ⅰ，Ⅲ型胶原分泌和Ⅰ/Ⅲ型胶原比值于伤后各时间点均显著低于对照组(P < 0.05)。模型组Ⅰ型胶原分泌与伤后7，14，21 d逐渐增加(P < 0.05)，Ⅲ型胶原于伤后21 d时分泌明显增高(P < 0.05)，Ⅰ/Ⅲ型胶原比值与伤后21 d时明显降低(P < 0.05)。结果证实，创面早期神经支配可以促进创面愈合，创面重塑期减轻神经支配可能会改善创面重塑质量。     

大鼠失神经支配后股骨密度变化的实验研究

目的　探讨大鼠失神经后骨密度变化的可能原因 ,以及NGF注射、电刺激和被动运动等治疗的应用价值 ,并为临床预防神经源性骨质疏松的治疗提供实验依据。方法　切断SD雄性大鼠坐骨神经和股神经 ,造成失神经支配大鼠模型 ,利用NOR LAND、XR 36型双能骨密度检测仪进行骨量测定。结果　大鼠失神经支配可引起骨密度的改变 ,通过NGF注射、电刺激和被动运动等治疗可减缓失神经大鼠的骨量下降 ,而失神经肢体的固定则加重了骨量的降低。结论　通过大鼠失神经后的骨密度变化 ,说明股骨密度在失神经支配后受多种因素的调控 ,其中力学因素是其首要和主要因素 ,同时大鼠失神经支配后 ,促进神经功能的重建以及维持神经再支配的生物学环境的稳定将有利于防止骨量的下降和骨质疏松的发生。     

大鼠失神经支配后股骨密度变化的实验研究

目的 探讨大鼠失神经后骨密度变化的可能原因，以及NGF注射、电刺激和被动运动等治疗的应用价值，并为临床预防神经源性骨质疏松的治疗提供实验依据。方法 切断SD雄性大鼠坐骨神经和股神经，造成失神经支配大鼠模型，利用NORLAND、XR-36型双能骨密度检测仪进行骨量测定。结果 大鼠失神经支配可引起骨密度的改变，通过NGF注射、电刺激和被动运动等治疗可减缓失神经大鼠的骨量下降，而失神经肢体的固定则加重了骨量的降低。结论 通过大鼠失神经后的骨密度变化，说明股骨密度在失神经支配后受多种因素的调控，其中力学因素是其首要和主要因素，同时大鼠失神经支配后，促进神经功能的重建以及维持神经再支配的生物学环境的稳定将有利于防止骨量的下降和骨质疏松的发生。     

间歇缺氧及睡眠剥夺大鼠血管内皮细胞相关指标的变化***☆

背景：血管内皮功能损坏是睡眠呼吸暂停的病理基础。 目的：观察间歇缺氧、睡眠剥夺对SD大鼠有创动脉收缩压及血浆一氧化氮、内皮素、降钙素基因相关肽水平的影响。 方法：将3月龄雄性SD大鼠16只随机等分为2组，模型组大鼠每天置入睡眠剥夺合并间歇性缺氧条件10 h (22：00-08：00)，单纯睡眠剥夺条件12 h(08：00-20：00)，剩余时间置大鼠笼饲养。对照组无睡眠剥夺、无缺氧条件饲养。 结果与结论：造模8周后，与对照组比较，模型组大鼠有创动脉压明显升高(P < 0.01)，血浆一氧化氮、降钙素基因相关肽水平显著降低(P < 0.01)，血浆内皮素水平显著升高(P < 0.01)。说明间歇性缺氧、睡眠剥夺可以引起SD大鼠血压增高，血管内皮功能受损。     

Toward noninvasive monitoring of ongoing electrical activity of human uterus and fetal heart and brain

Objective

To evaluate whether a full-coverage fetal-maternal scanner can noninvasively monitor ongoing electrophysiological activity of maternal and fetal organs.

Spatial patterns of visual cortical fast EEG during conditioned reflex in a rhesus monkey

A preliminary assay was made of the existence of time-space coherence patterns of fast EEG activity in the visual cortex of a Rhesus monkey. The primary intent of the present study was to evaluate the similarities and differences in relation to the olfactory bulb, where such coherences ave been described and have been demonstrated to be associated with behavior. Segments 1.5 s in duration were recorded simultaneously without averaging from 16 of 35 subdural electrodes fixed over the left occipital lobe in an array3.6cm× 2.8cm. Each segment was taken during the delivery of a visual conditioned stimulus (CS) and the performance of a conditioned response (CR) by a well-trained Rhesus monkey. The EEGs appeared chaotic with irregular bursts lasting 75–200 ms, resembling those in the olfactory EEG but with lower peak frequencies. Fourier spectra showed broad distributions of power resembling ‘ 1/fnoise’ with multiple peaks in the range of 20–40 Hz. Time intervals were selected where coherent activity seemed to be present at a number of electrodes. A dominant component waveform that was common to all channels was extracted by principal components analysis (PCA) of each segment. The distribution of the power of this component across the electrodes (the factor loadings) was used to describe the spatial pattern of the coherent cortical activity. Statistical analyses suggested that different patterns could be associated to the CS and the CR, as has been found in the olfactory system. These patterns remained stable over a 6 week recording interval. The patterns can be better discriminated, when the factor loadings of each channel are normalized to zero mean and unit variance, to discard a basic pattern of power distribution, which may reflect anatomical and electrode positioning factors that are related to behavioral information processing by the cortex. The wide spatial distribution of the common patterns found suggests that EEG patterns that manifest differing states of the visual cortex may also be accessible with scalp electrodes.     

Health consequences of acute and chronic marihuana use

Chemical content, assay procedures, and pharmacokinetics of cannabis sativa are discussed briefly. Cannabinoid cellular effects relating to chromosomes and immunity including cellular metabolism and allergic reactions are presented. Gross and microscopic brain pathology due to cannabis use is reviewed involving EEG alterations, psychopathology including aggressive behaviour as well as properties of psychomotor impairment, tolerance and dependence. Cardiopulmonary effects of marihuana are recorded under pulmonary pharmacological effects including the macrophage defense system and effects of smoke constituents; under cardiovascular effects cardiac toxicity and possible mechanism of action are discussed. Alterations of reproductive hormonal production and maturation of reproductive cells by marihuana in males and females with attendant impairment of reproductive function or fertility including reproductive outcome are reported. Field studies with healthy chronic cannabis users in Jamaica, Greece and Costa Rica are related as to observed medical alterations. Potential clinical effects are summarized in point form.     

Concentration of antiepileptic drugs in persons with epilepsy: a comparative study in serum and saliva

Aim of the study: The monitoring of antiepileptic drugs (AEDs) in clinical setting is important for measuring the efficacy of drugs and their safety and in personalizing drug therapy. We investigated the levels of AED, carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PHB), to understand their association in saliva compared with those in serum during the therapy. Materials and methods: In this study, we performed a prospective study of 116 persons with epilepsy (PWE; mean age 26.90 ± 11.83 years). Serum and saliva samples were collected at trough levels from the patients, who were under the treatment of CBZ, PHT and PHB either alone or in combination of these drugs for at least three months. The drug levels were assessed by high-performance liquid chromatography. Results and conclusions: The number of males (n = 88; 75.86%) was higher than females (n = 28; 24.14%) among the recruited patients. The intake of CBZ, PHT and PHB was observed in 49.14%, 68.10% and 38.79% of PWE, respectively. The levels of these AEDs showed a significant correlation (p < 0.05) between serum and saliva. Interestingly, the levels of mono-therapy or bi-therapy showed a significant association (p < 0.05) between serum and saliva, however, there was no significant association in case of poly-therapy. This is the first report in the Indian population on simultaneous estimation of the three commonly used AEDs, such as CBZ, PHT and PHB in serum and saliva implicating their associations, either in mono-therapy or bi-therapy in PWE.     

Do scalp-recorded slow potentials during neuro-feedback training reflect the cortical activity?

Objective

Neuro-feedback (NFB) training by the self-regulation of slow potentials (SPs) <0.5?Hz recorded from the vertex scalp has been applied for seizure suppression in patients with epilepsy. However, SP is highly susceptible to artifact contamination, such as the galvanic skin response (GSR). This study aimed to evaluate the correlation between SPs recorded from the scalp and intracranial electroencephalography (EEG) by event-related coherence analysis.

Rapid‐acting antidepressant ketamine,its metabolites and other candidates: A historical overview and future perspective

Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one‐third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists an unmet medical need for rapidly acting antidepressants with beneficial effects in treatment‐resistant patients with MDD or BD. Accumulating evidence suggests that the N‐methyl‐D‐aspartate receptor (NMDAR) antagonist ketamine produces rapid and sustained antidepressant effects in treatment‐resistant patients with MDD or BD. Ketamine is a racemic mixture comprising equal parts of (R)‐ketamine (or arketamine) and (S)‐ketamine (or esketamine). Because (S)‐ketamine has higher affinity for NMDAR than (R)‐ketamine, esketamine was developed as an antidepressant. On 5 March 2019, esketamine nasal spray was approved by the US Food and Drug Administration. However, preclinical data suggest that (R)‐ketamine exerts greater potency and longer‐lasting antidepressant effects than (S)‐ketamine in animal models of depression and that (R)‐ketamine has less detrimental side‐effects than (R,S)‐ketamine or (S)‐ketamine. In this article, the author reviews the historical overview of the antidepressant actions of enantiomers of ketamine and its major metabolites norketamine and hydroxynorketamine. Furthermore, the author discusses the other potential rapid‐acting antidepressant candidates (i.e., NMDAR antagonists and modulators, low‐voltage‐sensitive T‐type calcium channel inhibitor, potassium channel Kir4.1 inhibitor, negative modulators of γ‐aminobutyric acid, and type A [GABA_A] receptors) to compare them with ketamine. Moreover, the molecular and cellular mechanisms of ketamine’s antidepressant effects are discussed.     

Update of the original HDLS kindred: divergent clinical courses

Sundal C, Ekholm S, Nordborg C, Jönsson L, Börjesson‐Hanson A, Lindén T, Zetterberg H, Viitanen M, Andersen O. Update of the original HDLS kindred: divergent clinical courses.
Acta Neurol Scand: 2012: 126: 67–75.
© 2011 John Wiley & Sons A/S. Background – Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was first identified among a Swedish kindred with 17 cases. The average age of onset was 36 years. Autopsy in four cases revealed the presence of axonal spheroids. The causative gene is unknown. Methods – We performed genealogical and longitudinal observations of the original kindred. Forty members were examined, five telephone‐interviewed, and one of the original HDLS cases from 1984 was neuropathologically examined. The clinical course was documented. The cerebrospinal fluid (CSF) findings of two recently affected cases were examined, and one of those autopsied. Results – Of those examined, two developed HDLS during our survey and 38 were healthy. Those interviewed by telephone were healthy. One had symptoms suggestive of HDLS in 1984, but autopsy during our survey showed no spheroids. This patient, two relatives healthy at our examination and one without symptoms at telephone interview had HDLS diagnoses in the 1984 report. Thus, four HDLS diagnoses were unconfirmed. The number of identified patients amounts to 15 among 75 individuals in four generations, including two recent cases who demonstrated a subacute multisystem encephalopathy in Case 1 and an insidious course in Case 2. CSF showed signs of neurodegeneration without inflammation, and autopsy verified HDLS in Case 1. Conclusions – Some HDLS cases were misdiagnosed with unspecified psychiatric diagnoses in affected relatives from the original 1984 publication. However, HDLS is an encephalopathy dominated by a frontal lobe syndrome with an inexorably progressive and fatal course, where the different symptomatology in two recent cases confirmed the existence of acute and chronic variants.     

脑红蛋白在脑梗死大鼠表达及丁苯酞干预效应

目的探讨脑红蛋白在脑梗死大鼠中的表达和丁苯酞干预在氧化应激损伤中作用。方法将90只雄性SD大鼠随机分为假手术组、模型组、治疗组。每组再分为3个亚组:1 d组、3 d组和7 d组,每亚组10只。模型组和治疗组采用线栓法制作大鼠大脑中动脉闭塞模型(MCAO),假手术组只分离不结扎。治疗组在动物苏醒后以丁苯酞植物油灌胃,假手术组和模型组同法给予等量植物油灌胃。每只大鼠在术后3h和处死前行神经功能评分,应用RT-PCR和免疫组化检测脑组织脑红蛋白(NGB)表达,化学比色法检测超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果 (1)神经功能评分,模型组和治疗组术后3 h评分差异无统计学意义(P>0.05),各时间点处死前评分差异均有统计学意义(P<0.05)。(2)NGB mRNA和免疫组化表达随时间延长逐渐降低,各时间点模型组较假手术组、治疗组较模型组高,差异均有统计学意义(P<0.05)。(3)SOD活性和MDA含量随时间延长逐渐减少。SOD活性假手术组较治疗组、治疗组较模型组高,差异均有统计学意义(P<0.05);MDA含量假手术组较治疗组、治疗组较模型组低,差异均有统计学意义(P<0.05)。结论丁苯酞促进脑缺血大鼠脑红蛋白表达,减少氧化应激损伤。