汉防己甲素抑制三种神经递质引起的新生大鼠脑细胞内游离钙的升高

应用Ｐｕｒａ－２技术测定游离新生大鼠脑［Ｃａ２＋］ｉ浓度的技术、研究了Ｔｅｔ对静息脑［Ｃａ２＋］ｉ和３种递质引起的脑［Ｃａ２］ｉ变化的影响。Ｔｅｔ（１，１０和２０μｍｏｌ·Ｌ－１）对静息脑［Ｃａ２＋］ｉ无明显影响。Ｔｅｔ（１０μｍｏｌ·Ｌ－１）可降低Ｌ－Ｇｌｎ（０．１、１．０和１０μｍｏｌ·Ｌ－１）引起的脑（Ｃａ２＋）ｉ的升高。在Ｈａｎｋ＇ｓ液Ｃａ２＋为１．３ｍｍｏｌ·Ｌ－１时，Ｔｅｔ１０μｍｏｌ·Ｌ－１可降低Ｈｉｓ（５０和１００μｍｏｌ·Ｌ－１）和５－ＨＴ（０．１、１．０、１０和１００μｍｏｌ·Ｌ－１）引起的脑［Ｃａ２＋］ｉ的升高。但不能降低Ｈａｎｋ＇ｓ液无Ｃａ２＋时Ｈｉｓ和５－ＨＴ引起的脑［Ｃａ２＋］ｉ的升高。研究表明Ｔｅｔ可阻滞Ｌ－Ｇｉｎ、Ｈｉｓ和５－ＨＴ受体调控的钙通道。但对Ｈｉｓ和５－ＨＴ引起的细胞内贮存钙的释放并无明显影响。Ｔｅｔ的这种降低脑［Ｃａ２＋］ｉ的作用可能是其治疗脑缺血性疾病的机理之一。Ｐ＜０．０１在Ｔｅｔ１０μｍｏｌ·Ｌ－１作用下，相同浓度的细胞外液钙和Ｈｉｓ（０、５０和１００μｍｏｌ·Ｌ－１），脑［Ｃａ２＋］ｉ分别是２２１±５、２４５±５和３０２±６ｎｍｏｌ·Ｌ－１。增加了１１．８?     

Evaluation of neural fold fusion and coincident initiation of spinal cord occlusion in the chick embryo.

Although it is known that rapid expansion of the vertebrate brain begins near the time that the spinal neurocoel is occluded, it still remains unknown when occlusion occurs in relation to neurulation. Since both morphogenetic events are critical for normal brain growth, it is important to decipher the temporal relationship between the two processes. This study assessed the temporal relationship of the two events with the rationale that if it could be demonstrated that occlusion occurs coincident with the completion of neurulation, then it could be argued that factors shown to direct neurulation could also initiate occlusion. Nearly 600 chick embryos (stages 9- through 12+) were cultured atop egg-agar, the caudal extent of neurulation determined, the cranial five pairs of somites removed and the neurocoels assessed for occlusion. In stage 9- through 10- chicks, neurulation of the spinal cord is incomplete. Stages 10 through 12+ exhibit neurulation and occlusion from the 8th to 19th somites. When lateral tissues were removed in embryos 8 through 10-, the neural folds became dysraphic whereas in embryos stage 10 and older, the folds remained fused dorsomedially and occluded. The only surgical manipulation that was found to prevent occlusion was elimination of the lateral tissues responsible for elevation and closure of the neural folds. Analysis of particular components of the lateral tissues essential for convergence, by treating embryos (n = 75) with chemicals known to degrade tissue-tissue bonds or specific components of the perineural matrix, indicated that more than 75% of the embryos treated with EDTA, EDTA plus Ca2+, trypsin, collagenase, or hyaluronidase exhibited little or no effect on convergence, dorsomedial fusion, and concomitant occlusion.     

Thromboplastin—sensitivity,precision and other characteristics

A more sensitive or higher concentration of rabbit brain thromboplastin does not result in greater accuracy and precision of results in oral anticoagulant therapy and is unable to mimic the PIVKA sensitivity of human brain. In terms of International Normalized Ratios the British Comparative Thromboplastin and Manchester Comparative Reagent (both now discontinued) and the Manchester Reagent had the poorest sensitivity to factor VII of all the reagents studied. It is not possible accurately to calibrate rabbit brain against human brain thromboplastin in the upper therapeutic range and beyond.     

Saturation analysis of specific 11C Ro 15-1788 binding to the human neocortex using positron emission tomography

The ¹¹C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced ¹¹C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (B_max) and equilibrium dissociation constant (K_d) values on the basis of certain assumptions B_max values were in the order of 90 pmol/g and K_d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that ¹¹C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.     

Virulent and attenuated canine distemper virus infects multiple dog brain cell types in vitro.

Canine Distemper Virus (CDV) produces an encephalitis in dogs that varies with viral strain. We have studied the cell tropisms of two virulent strains (CDV-SH and CDV A75-17) and an attenuated strain, Rockborn (CDV-RO), in cultured canine brain cells. Infected cell types were identified by double immunofluorescent labeling of specific cell markers and viral antigens. All viral strains studied produced infection in astrocytes, fibroblasts, and macrophages. Neurons were not infected by CDV A75-17 but were rapidly infected by CDV-SH and CDV-RO. Multipolar oligodendrocytes were very rarely infected by any of the virus strains. In contrast, a morphologically distinct subset of bipolar oligodendrocytes were commonly infected by CDV-SH and CDV-RO. The kinetics of infection in the astrocytes, oligodendrocytes, neurons, and macrophages varied between strains. Both CDV-SH and CDV-RO rapidly infected bipolar oligodendrocytes, astrocytes, neurons, and macrophages by 14 days post infection while infection by CDV A75-17 was delayed until after 28-35 days post infection. The differences in the growth kinetics and cell tropisms for some brain cells, exhibited by the three viral strains examined in this in vitro study, may relate to the different CNS symptoms that these strains produce in vivo.     

子痫颅脑CT表现及与临床关系

目的分析子痫颅脑CT表现及与临床相关性。方法18例子痫患者均行颅脑CT平扫,其中3例行增强扫描,8例进行CT复查。结果14例患者显示脑白质内广泛低密度水肿区,枕叶脑白质累及为主,并多伴有额叶、顶叶受侵。4例表现为脑内局限性低密度区,2例合并脑出血,呈散在小斑片状分布。结论CT是子痫脑内病灶较好的影像检查手段,既可发现早期病灶,又可评价预后。     

Measurement of arterial input functions for dynamic susceptibility contrast magnetic resonance imaging using echoplanar images: comparison of physical simulations with in vivo results.

Measurement of the arterial input bolus shape is essential to the quantification of mean transit time and blood flow with dynamic susceptibility contrast (DSC) MRI. Input functions derived from the echoplanar signal intensity within or near arteries are highly nonlinear, yet such input functions are widely used. We employed a physical model for the echoplanar signal intensity from an artery as a function of contrast agent concentration, artery size, and angle to the magnetic field to test approaches for the measurement of the arterial input function. The simulated results confirmed the strong nonlinearity of signal in the neighborhood of vessels. Of the input function measurement methods considered, the simulations suggested that measurement of signal near but not within a large vessel is most accurate, but mean transit times (MTT) calculated with these input functions are highly sensitive to peak bolus concentration. Input functions determined from voxels demonstrating the shortest first moment overestimated the MTT but the measured MTTs were more robust to changes in peak concentration. Characteristics of the measured in vivo input functions were consistent with the simulations. Our results emphasize the important contribution of input function errors to the uncertainty in MTT and blood flow imaging with DSC MRI.     

Overactive bladder in Parkinson's disease: alteration of brainstem raphe detected by transcranial sonography

Urinary dysfunction is very common in idiopathic Parkinson's disease (PD) and manifests primarily with symptoms of overactive bladder (OAB). Affection of central serotonergic systems has been suggested to play a role in OAB. The objective of this study was to evaluate whether in PD patients with OAB symptoms a specific alteration of the brainstem raphe (BR), which contains serotonergic neurons, can be detected with transcranial sonography (TCS). Of 116 PD patients enrolled, 19 had PD-related OAB symptoms (OAB+) unlike remaining 97 patients (OAB−). Patients were examined by a sonographer blinded to the clinical data. Reduced echogenicity of BR was found in 12 (63%) OAB+ patients but only in 18 (19%) of 93 assessable OAB− patients (Mann–Whitney U -test, P  < 0.001). In OAB+ patients, lower raphe echogenicity score was associated with longer duration of OAB symptoms ( anova , P  = 0.033). Other TCS findings such as echogenicity of substantia nigra, thalami, lenticular and caudate nuclei, and widths of third and lateral ventricles did not differ between OAB+ and OAB− patients. TCS findings suggest a pathogenetic role of BR in OAB related to PD. Alterations may reflect disturbance of its central serotonergic system.     

Developmental changes of glutamate acid decarboxylase 67 in mouse brain after hypoxia ischemia

Objective To study the developmental changes of glutamic acid decarboxylase-67 (GAD-67, a GABA synthetic enzyme) in normal and hypoxic ischemic (HI) brain. Methods C57/BL6 mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature (P21, P60) and immature (P5, P9) brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia (HI) insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that (15.6±7.0)% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.