Restoration of microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit): Stimulatory effects of GH restricted to the first 20 days of postnatal life

We administered bovine growth hormone to the Little (lit), a promising model of isolated growth hormone deficiency, during the first and second 20 days after birth. Positive results were obtained only when bovine growth hormone was given during the first 20 days of postnatal life. We observed a distinct increase in cerebral weight, DNA content, and 2, 3-cyclic nucleotide 3-phosphohydrolase activity. The latter administration of bovine growth hormone was ineffective. These data prove that growth hormone has an independent action on cerebral development, apart from the complementary or synergistic action of thyroid hormones, and that the administration of exogenous growth hormone led to increased myelinogenesis through its stimulatory effects on glial proliferation, as evidenced by the increase in cerebral DNA content.     

5-Hydroxytryptamine Measurements in Molluscan Ganglia and Neurons Using a Modified Radioenzymatic Assay

A radioenzymatic procedure for the determination of sub-picomole amounts of 5-hydroxytryptamine (5-HT) is described. It is a modification of the method originally described by Saavedra et al. (1973), in which 5-HT was measured as the radiolabelled product [3H]5-methoxy-N- acetyltryptamine , after incubation with [3H]S-adenosylmethionine, acetyl-CoA, and the enzymes hydroxyindole-O-methyltransferase (EC 2.1.1.4) and N-acetyltransferase (EC 2.3.1.5). Ganglia from various gastropod molluscs (Aplysia californica, Tritonia diomedia , Lymnaea stagnalis, and Helisoma trivolvis ), as well as individual neuronal somata isolated from these ganglia, were assayed for 5-HT. Among the homologous giant cerebral cells in these animals, the 5-HT concentrations were similar. Statistical analysis of the 5-HT values in paired 5-HT-containing neurons demonstrated that the variability was considerably greater in samples obtained from different animals than in those obtained from the same animal. This suggests that experiments aimed at manipulating amine levels in individual neurons may benefit by using a paired-cell paradigm. The effects of incubating Aplysia ganglia with 5-HT or with the 5-HT precursors tryptophan and 5-hydroxytryptophan (5-HTP) were studied. High concentrations of 5-HTP and 5-HT (100 microM) increased the levels of 5-HT in ganglia, but only incubation in high concentrations of 5-HTP resulted in an increase of 5-HT in the isolated somata of 5-HT-containing neurons C1 and P5.     

小骨窗微创手术治疗高血压脑出血患者的疗效

目的:分析小骨窗微创手术在高血压脑出血患者的临床效果。方法:选取我院收治的高血压脑出血患者200例,按照治疗方式的不同分为观察组100例,对照组100例,观察组采用小骨窗微创手术治疗,对照组采用传统开颅手术治疗,对两组疗效及预后进行对比。结果:两组患者的术后残留血肿量较术前明显减少,差异有统计学意义(P0.05),观察组术后残留血肿量(10.3±2.8)m L,对照组术后残留血肿量(11.1±3.0)m L,两组之间术后血肿残留量比较,差异无统计学意义(P0.05)。观察组手术时间(92.8±15.5)分钟,对照组手术时间(125.4±16.1)分钟,观察组手术时间明显短于对照组,差异有统计学意义(P0.05)。观察组住院时间(15.8±5.2)天,对照组住院时间(24.1±5.8)天,观察组住院时间明显短于对照组,差异有统计学意义(P0.05)。再出血率比较:观察组治疗后再出血率3.0%,对照组治疗后再出血率8.0%,观察组出血率明显低于对照组,差异有统计学意义(P0.05)。NDS及ADL比较:两组治疗后NDS及ADL均优于治疗前,差异有统计学意义(P0.05)。观察组NDS及ADL均显著优于对照组,差异有统计学意义(P0.05)。GCS比较:两组评分差异无统计学意义(P0.05)。结论:小骨窗微创手术可以改善患者的预后,可显著提高高血压脑出血治疗效果。     

降纤酶治疗急性脑梗塞的疗效及对血浆纤维蛋白原的影响

目的:研究降纤酶治疗急性脑梗塞的疗效以及对血浆纤维蛋白原的影响。方法:选取2010年4月到2014年6月我院收治的急性脑梗塞患者130例,按照随机数字表法将患者分为研究组和对照组,每组65例,两组均给予常规治疗,对照组在常规治疗的基础上给予安慰剂,研究组给予降纤酶,比较两组临床疗效、神经功能缺损评分、血浆纤维蛋白原水平以及不良反应。结果:研究组总有效率为95.4%,显著高于对照组的76.9%(P0.05);治疗后研究组神经功能缺损评分与治疗前和对照组比较差异具有统计学意义(P0.05);治疗后研究组血浆纤维蛋白原显著低于治疗前和对照组(P0.05);两组不良反应比较差异无统计学意义(P0.05)。结论:降纤酶治疗急性脑梗塞具有较好的临床疗效,改善患者的神经功能,降低血浆纤维蛋白原。     

阿米洛利对脑梗死急性期患者血清炎症因子水平的影响

目的:探讨阿米洛利对脑梗死急性期患者血清ox-LDL、炎症因子及MMP-9水平影响及其意义。方法:选取我院诊治的急性脑梗死患者120例,随机分为对照组和实验组,每组60例。两组患者均给予常规对症治疗,实验组在对照组的治疗基础上加用盐酸阿米洛利片。采用酶联免疫吸附法(ELISA)及免疫透射比浊法分别测定两组患者血清ox-LDL、炎症因子及MMP-9水平,并对患者神经功能缺损程度进行评分。结果:治疗后,两组患者神经功能均较治疗前明显改善,且实验组明显优于对照组,差异均具有统计学意义(P0.05);治疗后,两组患者血清ox-LDL及MMP-9水平均低于治疗前,且实验组低于对照组,差异具有统计学意义(P0.05);治疗后,两组患者血清炎症因子TNF-α、IL-6及hs-CRP水平均低于治疗前,且实验组低于对照组,差异具有统计学意义(P0.05)。结论:阿米洛利能够降低脑梗死急性期患者ox-LDL、TNF-α、IL-6、hs-CRP及MMP-9水平,减轻炎症反应,改善患者的神经功能。     

血栓通注射液对急性脑出血患者血清IL-8、IL10 水平的影响

目的:探讨血栓通注射液对急性脑出血患者血清IL-8、IL10以及与颅内血肿水平影响及临床意义。方法:选取我院收治的急性脑出血患者80例,随机分为对照组及实验组,对照组以常规消肿治疗,实验组在对照组基础上予以血栓通注射液活血消肿治疗。比较各组患者治疗前后IL-8、IL-10、TNF-α、CRP水平、颅内血肿面积、层数和低密度影像水平以及NIHSS功能评分变化情况。结果:与治疗前比较,两组患者IL-8、IL-10、TNF-α、CRP及颅内血肿水平均降低(P0.05);与对照组相比较,实验组患者治疗后IL-8、IL-10、TNF-α、CRP及颅内血肿水平较低(P0.05);NIHSS功能评分较高,差异具有统计学意义(P0.05)。结论:血栓通注射液可改善急性脑出血患者血肿周围脑组织水肿状态及炎性反应状态,降低炎性因子及坏死因子的释放,改善病灶区脑组织血液循环,可作为临床有效治疗方案。     

苯肼对实验性脑疟模型DC亚群及功能的影响

探讨苯肼(Phenylhydrazine,PHZ)对实验性脑疟模型DC亚群及功能的影响。采用伯氏疟原虫(Plasmodium berghei ANKA,Pb ANKA)感染C57BL/6小鼠建立实验性脑疟模型,并在感染前第5天和感染第0天进行苯肼处理。动态监测小鼠网织红细胞数量、原虫血症和生存期;采用FACS检测感染后第3天和第5天小鼠脾脏中DC亚群(m DCs和p DCs)及相关功能分子(CD86、MHC II和IL-2)的变化水平。结果显示,PHZ处理能显著升高血液中网织红细胞比例,同时会升高小鼠原虫血症水平,缩短生存期;在感染后第3天和第5天,PHZ处理能促进Pb ANKA感染小鼠m DCs和p DCs的增殖分化,并能增强MHC II类分子和胞内IL-12的表达水平。PHZ引起的贫血能促进DCs的分化,同时促进功能分子的表达升高来启动适应型免疫应答,促进脑疟发生。     

Synergistic induction of CXCL10 by interferon-gamma and lymphotoxin-alpha in astrocytes: Possible role in cerebral malaria

Cerebral malaria (CM) has a high mortality rate and incidence of neurological sequelae in survivors. Hypoxia and cytokine expression in the brain are two mechanisms thought to contribute to the pathogenesis of CM. The cytokines interferon (IFN)-γ and lymphotoxin (LT)-α and the chemokine CXCL10 are essential for the development of CM in a mouse model. Furthermore, serum IFN-γ protein levels are higher in human CM than in controls, and CXCL10 is elevated in both serum and cerebrospinal fluid in Ghanaian paediatric CM cases. Astrocytes actively participate in CNS pathologies, becoming activated in response to various stimuli including cytokines. Astrocyte activation also occurs in murine and human CM. We here determined the responsiveness of mouse and human astrocytes to IFN-γ and LT-α, with the aim of further elucidating the role of astrocytes in CM pathogenesis. Initially we confirmed that Ifn-γ and Cxcl10 are expressed in the brain in murine CM, and that the increased Cxcl10 expression is IFN-γ-dependant. IFN-γ induced CXCL10 production in human and murine astrocytes in vitro. The degree of induction was increased synergistically in the presence of LT-α. IFN-γ induced the expression of receptors for LT-α, while LT-α increased the expression of the receptor for IFN-γ, in the astrocytes. This cross-induction may explain the synergistic effect of the two cytokines on CXCL10 production. Expression of these receptors also was upregulated in the brain in murine CM. The results suggest that astrocytes contribute to CM pathogenesis by producing CXCL10 in response to IFN-γ and LT-α.     

Ablation of the 14‐3‐3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex

14‐3‐3 proteins are ubiquitously‐expressed and multifunctional proteins. There are seven isoforms in mammals with a high level of homology, suggesting potential functional redundancy. We previously found that two of seven isoforms, 14‐3‐3epsilon and 14‐3‐3zeta, are important for brain development, in particular, radial migration of pyramidal neurons in the developing cerebral cortex. In this work, we analyzed the function of another isoform, the protein 14‐3‐3gamma, with respect to neuronal migration in the developing cortex. We found that in utero 14‐3‐3gamma‐deficiency resulted in delays in neuronal migration as well as morphological defects. Migrating neurons deficient in 14‐3‐3gamma displayed a thicker leading process stem, and the basal ends of neurons were not able to reach the boundary between the cortical plate and the marginal zone. Consistent with the results obtained from in utero electroporation, time‐lapse live imaging of brain slices revealed that the ablation of the 14‐3‐3gamma proteins in pyramidal neurons slowed down their migration. In addition, the 14‐3‐3gamma deficient neurons showed morphological abnormalities, including increased multipolar neurons with a thicker leading processes stem during migration. These results indicate that the 14‐3‐3gamma proteins play an important role in radial migration by regulating the morphology of migrating neurons in the cerebral cortex. The findings underscore the pathological phenotypes of brain development associated with the disruption of different 14‐3‐3 proteins and will advance the preclinical data regarding disorders caused by neuronal migration defects. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 600–614, 2016     

Image‐derived arterial input function for quantitative fluorescence imaging of receptor‐drug binding in vivo

Receptor concentration imaging (RCI) with targeted‐untargeted optical dye pairs has enabled in vivo immunohistochemistry analysis in preclinical subcutaneous tumors. Successful application of RCI to fluorescence guided resection (FGR), so that quantitative molecular imaging of tumor‐specific receptors could be performed in situ, would have a high impact. However, assumptions of pharmacokinetics, permeability and retention, as well as the lack of a suitable reference region limit the potential for RCI in human neurosurgery. In this study, an arterial input graphic analysis (AIGA) method is presented which is enabled by independent component analysis (ICA). The percent difference in arterial concentration between the image‐derived arterial input function (AIF_ICA) and that obtained by an invasive method (ICA_CAR) was 2.0 ± 2.7% during the first hour of circulation of a targeted‐untargeted dye pair in mice. Estimates of distribution volume and receptor concentration in tumor bearing mice (n = 5) recovered using the AIGA technique did not differ significantly from values obtained using invasive AIF measurements (p = 0.12). The AIGA method, enabled by the subject‐specific AIF_ICA, was also applied in a rat orthotopic model of U‐251 glioblastoma to obtain the first reported receptor concentration and distribution volume maps during open craniotomy.