A VEP investigation of parallel visual pathway development in primary school age children

Different features of visual function mature along unique timescales through infancy and early childhood. It is not clear which functions continue to mature in school age children. Functions believed to be mediated by the Magnocellular (M) and Parvocellular (P) pathways were compared in five- (n=25), eight- (n=21) and eleven-year-old children (n=21) and young adult controls (n=20). Steady-state visual evoked potentials were recorded from occipital electrodes in response to very low spatial frequency gratings, at a series of contrasts (M), and to high contrast gratings at a series of spatial frequencies (P). No evidence was found to indicate M pathway development across these age groups. However, the youngest children demonstrated elevated VEP thresholds to the high contrast gratings compared with either the adults or eleven-year-olds. This difference in threshold implies an immaturity of the high contrast, high spatial frequency stream, i.e. the putative P pathway. This revised version was published online in July 2006 with corrections to the Cover Date.     

Role of tachykinins in airway narrowing induced by cigarette smoke in guinea pigs

To investigate the mechanism of the airway narrowing induced by cigarette smoke, anaesthetized guinea pigs were exposed to 200 puffs of smoke for 10 min. Airway narrowing was assessed by monitoring the total pulmonary resistance (R_L). Plasma extravasation was determined by measuring the amount of Evans blue dye extravasated into the trachea and main bronchi. Exposure to cigarette smoke caused a marked airway narrowing and plasma extravasation. Pretreatment with the dual NK₁ and NK₂ receptor antagonist, FK224, abolished such airway narrowing and significantly inhibited the extravasation. While the NK₁ receptor antagonist, FK888, inhibited the extravasation, it had no effect on airway narrowing. Atropine partially inhibited airway narrowing without affecting extravasation. Results suggest that the airway narrowing induced by cigarette smoke is caused by tachykinins, and that a cholinergic pathway is involved. Thickening of the airway walls induced by NK₁ receptor-mediated extravasation may not be involved in such airway narrowing.     

Hemispherectomy — 25 years later — findings and concepts

Summary In the first part the case of a then 27 year old female patient with right-sided infantile spastic hemiplegia after left-sided porencephaly is described, in whom hemispherectomy was performed 25 years ago. The postoperative state and the development are described as well as the social outcome and the present neurological status. A computer-tomogram shows the actual state of the brain.The second part is devoted to a scientific discussion of the supplementary motility after pyramidal lesions which is defined as the action of descending subcortico-spinal pathways starting probably in the mesencephalon, whereas an ipsilateral pathway is unlikely. Comparative neurological experiments serve to support such a concept as well as similar observations in traumatic cerebral lesions in man. In the light of the far more skilled motility in cerebral lesions of the young as well as the possibility of a shift of neuropsychological functions of the dominant to the contralateral hemisphere in children up to the age of 8–10 the possibility is discussed that plasticity — the concept of Albert Bethe — could form the mechanism of auxiliary function.Furthermore the surprising sensory performances in some of the patients with hemispherectomy are emphasized and the possibilities of anipsilateral substratum are discussed; however, this contrasts with the concepts formulated for the auxiliary motility after pyramidal lesions. Clarification of these problems will probably follow only after further experimental work.

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Zusammenfassung Im ersten Teil der Arbeit wird der Fall einer damals 27-jährigen Patientin beschrieben, die eine rechtsseitige infantile spastische Hemiplegie nach linksseitiger Porencephalie hatte. Bei ihr war 25 Jahre zuvor eine Hemisphärektomie durchgeführt worden. Der postoperative klinische Status und die Entwicklung der Syndrome wird beschrieben und über die soziale Situation berichtet. Schließlich wird der derzeitige neurologische Status genau wiedergegeben. Erstmalig zeigt ein Computer-Tomogramm den Zustand des Hirns nach diesem Zeitraum.Im zweiten Teil der Arbeit wird die Entstehung der Ersatz-Motilität diskutiert, die als eine Aktion deszendierender subkortiko-spinaler Bahnen definiert wird, die wahrscheinlich vom Mittelhirn ihren Ausgang nehmen, während die Tätigkeit ipsilateraler Systeme für unwahrscheinlich gehalten wird. Vergleichende Tierexperimente am Hirn unterstützen eine solche Auffassung, ebenso wie auch die Beobachtung bei umschriebenen Hirnverletzungen des Menschen.Dann wird die Möglichkeit von Ersatzfunktionen durch Plastizität diskutiert — ein Begriff von Albert Bethe. Dies erscheint im Lichte vieler Beobachtungen wichtig, da die Ersatz-Motilität bei Hirnläsionen junger Menschen sehr viel höhere Geschicklichkeit ermöglicht als bei Läsionen von Älteren; weiter ist zu beachten, daß neuropsychologische Funktionen bei einer Hirnläsion vor dem 8. bis 10. Lebensjahr von einer dominanten Hemisphäre noch auf die andere Seite verlegt und dort lokalisiert werden können. Schließlich wird bei diesen Patienten auf die erstaunlichen Fähigkeiten der sensiblen Systeme nach Hemisphärektomie hingewiesen und hier die Möglichkeit eines ipsilateralen anatomischen Apparates diskutiert. Jedoch können bei der Sensibilität so genaue funktionell-morphologische Vorstellungen noch nicht formuliert werden, wie sie sich z. Zt. schon für die Ersatz-Motilität nach Pyramidenbahnläsion ergeben. Erst genauere Experimente im Tierversuch können weitere Aufklärung bringen.

     

Pharmacological interactions with circling behaviour induced by the piperidinyl indole derivative RU 23686

When administered i.p. from doses of 10 mg/kg, RU 23686 [5-methoxy 3-(4-piperidinyl) 1H-indole hydrochloride], a drug with relatively weak stimulant properties, induces contralateral (C) circling behaviour in rats with a unilateral electrolytic lesion in the striatum and a more complex effect with ipsilateral (1) and/or C circling in rats with a 6-hydroxydopamine (6-OHDA) lesion in the dopamine (DA) nigro-striatal tract. Interactions of RU 23686 with pharmacological agents have been studied in order to investigate the extent to which different neurotransmitters may be implicated in the circling behaviour induced by this compound.In striatal of 6-OHDA lesioned rats, methyl p-tyrosine (MT) did not modify C turns, while in the latter case only I turns were decreased. FLA 63, propranolol, and desipramine were also inactive in rats with a unilateral striatal lesion. Haloperidol reduced the effects of a 10 mg/kg dose of RU 23686 in striatal lesioned rats but was without effect against a dose of 20 mg/kg; in 6-OHDA lesioned rats, haloperidol blocked induced I turns but either did not affect or increased C turns. Phenoxybenzamine and p-chlorophenylalanine (PCPA), but not methysergide, p-chloroamphetamine (PCA), or fluoxetine, reduced the effect of RU 23686 in rats with a striatal lesion. In nigro-striatal lesioned rats, PCPA exhibited a differing effect according to the predominance of I or C turns: in rats with a mainly C response, C turns were decreased and I turns preserved, whereas in rats with a majority of I responses, these were depressed. In both types of lesions, animals reserpinized 48 h before RU 23686 exhibited an increase in their C circling, even in 6-OHDA lesioned animals where I turns predominated. In both rotational models, apomorphine-induced circling was potentiated by RU 23686.It is concluded that I circling, which is blocked by haloperidol and MT, could be related to a presynaptic action causing DA release. On the other hand, C turns do not depend on apomorphine-sensitive DA receptors in the striatum. A minor or indirect role of 5-hydroxytryptamine (5-HT) containing areas is suggested from the response to PCPA and the lack of effect of other drugs interfering with 5-HT. Results obtained from interactions with phenoxybenzamine, caffeine, and reserpine and the bimodal response to RU 23686 observed in 6-OHDA lesioned rats could indicate an interference with adrenergic processes.     

金丝桃素光动力学疗法与其诱导细胞凋亡、抗凋亡信号转导系统

金丝桃素在光诱导下产生活性氧，利用其光动力学治疗(PDT)在肿瘤细胞中显示出细胞毒作用，能以浓度和光依赖的方式诱导肿瘤细胞产生凋亡与坏死；通过细胞凋亡、抗凋亡信号转导通路调节细胞死亡程序。临床上利用PDT的金丝桃素被认为是安全、有效的新型抗肿瘤药物。     

曲古抑菌素A对前列腺癌LNCaP细胞雄激素受体的清除作用

目的:研究组蛋白去乙酰化酶抑制剂曲古抑菌素A(trichostatinA,TSA)对前列腺癌细胞的抑制作用机理。方法:四甲基偶唑氮蓝(MTT)检测药物对肿瘤细胞增殖的影响;Hochest33342染色观察细胞凋亡的形态学变化;Western印迹分析雄激素受体(AR)蛋白的表达;反转录PCR检测AR转录水平的变化。结果:TSA在较低浓度即能有效抑制LNCaP细胞的增殖,EC50为125.9nmol·L-1,并诱导肿瘤细胞凋亡;药物处理后细胞周期依赖性蛋白激酶抑制剂p21表达增高,AR呈时间及剂量依赖性被清除。TSA对AR的清除是发生在蛋白水平的降解,而不影响其转录。结论:TSA能够清除对细胞生长具有重要作用的AR细胞信号通路,从而对前列腺癌LNCaP细胞发挥抑制作用。     

Mononuclear cell proliferation and hyperplasia during Wallerian degeneration in the visual system of the goldfish in the presence or absence of regenerating optic axons

Patterns of proliferation and changes in non-neuronal cell number in the visual system of the goldfish have been quantitatively examined during optic axon regeneration after an optic nerve crush (ONC). In addition, in order to examine the effect of the regenerating axons on cellular responses in the visual pathways, we did a similar analysis of animals with the right eye removed (ER). Finally, we used double labeling protocols to demonstrate that the proliferating cells that we were counting were mostly phagocytic cells of the mononuclear lineage. In animals with an ONC, we observed an early burst of proliferation that peaked between 7 and 14 days after surgery in all parts of the visual system. In the optic tract, there was also a secondary rise that peaked at 21 days. Levels of proliferation returned to normal by 32 days postoperative in the tract and tectum, while they remained somewhat elevated in the optic nerve for at least 93 days. The total number of non-neuronal cells in the visual paths also rose to peak values between 7 and 14 days after ONC surgery. In the optic tract and tectum, the values fell rapidly after this time, while in the optic nerve, there was a secondary peak at 32 days after which values remained elevated for the duration of the experiment. As compared to animals with an ONC, enucleation resulted in elevated proliferation and hyperplasia at early postoperative intervals. However, because these differences occurred when axons had not yet regenerated into the affected structures, these data do not provide strong evidence for a direct effect of regenerating optic axons on the early cellular responses during Wallerian degeneration in the goldfish. In addition, in the tectum, there was an early increment in cell number that was not associated with elevated levels of proliferation. We believe that this increment represents immigration of resident microglia from other regions of the brain.     

应用神经轴突示踪技术研究人类视觉神经通路胚胎发育

目的 :应用神经轴突示踪方法 ,研究人类视觉神经通路在胚胎期 12w时的发育情况。方法 :取 12w胎龄的胚胎 ,浸泡在 4 %的甲醛缓冲液中固定后 ,分别在视束、上丘臂和视皮质下植入DiI染料 (DiI,1,1’ dioctadecyl 3,3,3’ ,3’ tetramethylin docarbocyanineperchlorate)。于室温下放置 4w ,待DiI晶体充分扩散后 ,根据神经轴突方向切片 ,通过共焦激光扫描显微镜观察并记录结果。结果 :大体标本观察可见到 ,视网膜神经纤维投射已到达外侧膝状体、上丘。切片观察发现 :外侧膝状体处尚未出现分层现象 ;上丘处 ,来自视网膜的神经纤维位于上丘臂的背侧 ;视皮质下已存在板层结构 ,板层内神经元呈多种形态。结论 :通过神经轴突示踪技术发现 ,12w时视网膜的神经纤维投射已经到达外侧膝状体和上丘 ,视皮质下存在板层结构。这说明人类视觉神经通路发育存在“等待期”。     

腹部手术影响小肠平滑肌细胞收缩的细胞内信号转导机制研究

目的:探讨腹部手术操作对小肠平滑肌细胞收缩功能的影响及细胞内信号转导途径。方法:采用Wistar大鼠制作腹部手术动物模型,酶解法获取小肠游离环行平滑肌细胞,检测平滑肌细胞在乙酰胆碱作用下的收缩反应和胞浆游离钙离子浓度([Ca2 ]i)的变化,然后将细胞分别与一氧化氮合酶抑制剂L-NNA、钙活化的K 通道阻滞剂A-pamin、蛋白激酶A抑制剂H89和蛋白激酶G抑制剂KT5823等一同孵育,重复以上实验过程。测定小肠环行平滑肌细胞培养24 h后培养基中一氧化氮(NO)的含量。结果:培养24 h后,实验组小肠环行平滑肌细胞产生的NO量明显高于对照组(P<0.05),L-NNA可明显降低实验组NO的产量,而对照组NO产量没有明显影响;L-NNA和KT5823可明显提高实验组小肠环行平滑肌细胞的收缩能力及乙酰胆碱刺激的[Ca2 ]i升高的水平(P<0.05),而Apamin和H89没有明显的影响。结论:腹部手术操作导致小肠肌层大量生成NO,激活鸟苷酸环化酶产生cGMP,通过PKG途径降低细胞内[Ca2 ]i的水平,抑制小肠平滑肌细胞的收缩能力。