转化生长因子β1在脑积水发生中的作用

脑积水是以脑脊液流动障碍和脑萎缩为主要特点的神经系统疾病.遗传突变、先天性畸形、感染、颅内出血和肿瘤等均能导致不同程度的脑积水.转化生长因子β1(TGF-β1)是脑发育过程中一种重要的生长因子,该基因过表达小鼠可通过调节基质金属蛋白酶-9和基质金属蛋白酶组织抑制剂-1的表达,改变细胞外基质环境,从而导致脑积水形成.本文就TGF-β1在脑积水发生中的作用做一综述.     

NJS—7型多功能脑积水分流装置研制成功

由苏州医学院附属一院、常州市第一人民医院、上海华山医院、上海橡胶制品研究所、上海医疗器械研究所和苏州第一轻工机械厂共同研制的NJS—7型多功能脑积水分流装置于去年底通过鉴定。该装置适用于各种脑积水患者施行脑室——腹腔(或心房)分流术,埋藏在体内起到分流脑脊液、减低颅内压力的作用。它由注液泵、压差阀、抗虹吸阀、开关阀、脑室引流管及腹腔管(或心房管)等部件组成,并按流     

自发性脑出血并发消化道出血的临床分析

目的:对自发性脑出血(ICH)后出现的消化道出血的致病因素以及应对激性溃疡常用预防措施(SUP)进行分析。方法:对2011年1月至2013年12月期间医院急诊科和神经内科的808例ICH治疗案例资料做了回顾性分析,这当中有216例ICH患者出现消化道出血;592例ICH患者未出现消化道出血。分析:对引发消化道的致病因素进行了Logistic回归分析。结果:在ICH患者当中,消化道出血的发病概率是26.7%,这当中有3例(占0.35%)属于严重消化道出血。发生消化道出血的病人无论是住院时间还是死亡率都比未出现消化道出血的病人要高,统计差异具备统计学意义(P0.05或P0.01)。对出现消化道出血和未出现消化道出血的两组病人在年龄结构、以往是否发生过消化道性溃疡或消化道出血、是否存在肾功能不全、GCS评分、患者出血部位、血肿体积、是否破人脑室和是否存在脓毒症等进行对比,统计差异具备统计学意义(P0.05或P0.01)。未出现消化道出血的患者总计512人都接受了SUP。结果显示,接受SUP的病人发生消化道出血的概率明著要比没有接受SUP患者的高,统计差异具备高度统计学意义(P0.01)。3多因素Logistic回归分析表明,患者年龄、血肿体积大小、患者的GCS评分,以及是否发生脓毒症都成为消化道出血的独立预测因子。结论:在发生ICH后出现消化道出血具有较高概率,发生严重消化道出血的概率不高。患者年龄、血肿体积大小、患者的GCS评分,以及是否发生脓毒症构成了消化道出血的独立预测因子,作为消化道出血的预防措施SUP的具有的价值尚需做深入探讨。     

脑室出血合并脑积水行脑室外引流高危因素的临床分析

目的:探讨脑室出血后未立即行脑室外引流术发生脑积水的指征和时机。方法:回顾性分析2009年1月到2015年9月我院收治的98例脑室内出血患者的临床资料。结果:98例患者中,28例(28.6%)患者需要行脑室外引流术。全脑室出血是最常见的类型(49例,50%),这些患者中24例(49%)需要行脑室外引流术。在脑室外引流术组和非脑室外引流术组平均m GS分别是17±5.1(12-28)和8±4.2(2-20)(P0.001)。与脑室外引流术相关的因素包括影像学表现为脑积水、中线移位5 mm、GCS评分8分、m GS13分、三脑室m GS=5及四脑室m GS=5分。多因素回归分析中,m GS13分、GCS评分8分和四脑室m GS=5分仍是重要的影响因素。大部分患者(24例,85.7%)在有脑积水症状时很快行脑室外引流术,有4例患者在48小时后行脑室外引流术。结论:昏迷、m GS13分和四脑室扩大使行脑室外引流术的风险增大。大部分患者在脑室出血后一天内行脑室外引流术,很少一部分患者在48小时后行脑室外引流术。     

多纤毛细胞纤毛精确组装的调控机制

高等动物体内气管、脑室管膜及输卵管等上皮组织具有一类富含运动纤毛的多纤毛细胞,通过其细胞表面运动纤毛的周期性摆动可以清洁气管、驱动脑脊液流动和受精卵运动.运动纤毛发生或功能的异常则可导致气管炎、脑积水、不孕不育等多种遗传疾病.然而,在多纤毛细胞分化过程中关于如何精确组装运动性纤毛复杂结构的分子机制仍不清楚.该研究运用蛋...     

一组有或无CT 脑灌注" 点征"的自发性脑内出血患者临床效果观察

目的:观察有或无CT脑灌注"点征"自发性脑内出血(sICH)患者的临床疗效。方法:以本院2013年5月~2015年5月就诊的100例s ICH,均接受基线CT脑灌注检查,依据是否有"点征"将患者分为观察组(有"点征")与对照组(无"点征"),24内行CT平扫复查,比较两组影像学结果及临床结果。并通过Logistic多因素分析影响s ICH患者预后不良(死亡)危险因素。结果:观察组24h内CT平扫复查血肿增长6 mL以上、血肿增长相对值33%及以上比率均明显高于对照组(P0.05);观察组血肿进展发生率、3个月内死亡率分别为63.04%、36.96%,显著高于对照组的14.81%、7.41%(P0.05)。Logistic回归分析发现sICH患者预后不良独立危险因素包括基线血肿体积、"点征"。结论:有或无CT脑灌注"点征"自发性脑内出血患者血肿进展、预后不同,基线血肿体积、"点征"为sICH患者预后不良的独立危险因素。     

感染与早产儿脑损伤临床关系探讨

目的:探讨感染与早产儿脑损伤(HIE,ICH,CWMD)的临床表现,治疗,预后和预防的关系。方法:对2000年1月-2006年10月214例早产儿进行临床分析。结果:胎膜早破32例,母亲妊高症23例,胎儿宫内窘迫33例,脐带扭转打结7人,母亲妊娠糖尿病4人,胎儿畸形4人;早产儿肺炎101人,早产儿寒冷损伤综合征7人,早产儿急性坏死性小肠结肠炎5人,低血糖症27人,低血钙症13人,早产儿缺氧缺血性脑病(HIE)76人,早产儿颅内出血(ICH)21人,早产儿脑白质损伤(CWMD)3人。早期诊断、合理抗感染治疗可减少早产儿HIE及ICH以及CWMD患儿的神经系统后遗症。结论:早产儿感染与HIE及ICH以及CWMD的关系密切,预防产前、产时、产后感染对减少或减轻早产儿脑损伤至关重要。     

脑出血后白质损伤分子机制和治疗研究进展

脑出血(intracerebral hemorrhage, ICH)是临床上常见的卒中类型,具有高致残率、高死亡率特点。由于高血压合并细小动脉硬化、血液病或脑血管淀粉样变等病因,血液自破裂的血管溢出,血肿压迫且大量毒性代谢产物可直接损伤脑实质,造成中枢神经系统功能缺陷。中枢神经系统包括灰质与白质,灰质由神经元胞体和树突组成,白质由髓鞘包覆的神经轴突和少突胶质细胞组成。目前,ICH的研究多集中于灰质损伤的机制,而针对白质损伤(white matter injury, WMI)的研究仍处于起步阶段,这或是临床使用神经元退行性变保护剂治疗失败的原因之一。近年来,研究人员已确定占位效应、神经炎症、氧化应激等病理生理机制是ICH后WMI的原因,但其分子机制尚未阐明,故针对ICH后WMI的治疗手段亦不成熟。在本文中,我们将简述白质的结构与功能,总结WMI的病理改变,并重点讨论ICH后WMI的分子机制和治疗研究进展。     

肥厚型心肌病患者认知功能障碍的发生及影响因素分析

目的:探讨肥厚型心肌病(HCM)患者认知功能障碍的发生及影响因素。方法:收集2018年4月至2019年7月期间空军军医大学第一附属医院超声医学科HCM患者198例。综合北京版蒙特利尔认知评估(MoCA)量表结果及教育程度,判断患者认知功能:文盲且MoCA得分14分、1年≤教育年限≤6年且MoCA得分20分、或教育年限6年且MoCA得分25分为认知功能障碍组(n=37),其余为认知功能正常组(n=161)。比较两组患者一般资料、超声心动图检查结果及认知功能评估结果。采用多因素logistic回归分析筛选HCM患者认知功能障碍的可能危险因素。结果:HCM患者认知功能障碍的发生率为18.7%(37/198)。与认知功能正常组相比,认知功能障碍组HCM患者年龄较大(P0.05),受教育年限较短(P0.05),心功能分级及左心室舒张功能较差(P0.05),激发左心室流出道压差较高(P0.05)。认知功能障碍组HCM患者MoCA得分较低(P0.05),尤其在视空间与执行功能和延迟回忆(P0.05)两项上得分较差。多因素logistic回归分析结果表明,调整年龄(OR=14.435, 95%CI:4.476-46.550; P0.001)和教育年限(OR=5.274, 95%CI:2.024-13.744; P=0.001)后,激发左心室流出道压差(OR=3.844, 95%CI:1.551-9.524; P=0.004)是HCM患者认知功能障碍的独立危险因素。结论:激发左心室流出道压差可以增加HCM患者认知功能障碍的发生风险。     

大鼠脑出血后大脑凝血酶受体-1长时效动态表达变化

目的:探讨脑出血(ICH)后凝血酶受体的动态及长时效表达。方法:将36只大鼠随机分为6组(n=6):正常组,ICH模型6h、24h、3d、7d和14d组。Ⅶ-S型胶原酶诱导大鼠ICH模型。免疫组化方法测定不同时间点大鼠ICH后血肿周围水肿组织PAR-1蛋白的表达;RT-PCR方法检测蛋白酶激活的受体(PAR)-1mRNA的表达。结果:正常组大鼠大脑PAR-1蛋白和PAR-1mRNA表达轻度阳性,模型组6h时PAR-1表达强度开始增强,24hPAR-1表达进一步增强,于3d达到高峰,然后开始下降,7d时明显下降,14d进一步下降,但仍未至正常组水平。模型组各时间点PAR-1阳性细胞数、PAR-1mRNA吸光度比值升高与正常组比较均有显著性差异(P<0.05或P<0.01)。此外,PAR-1蛋白在脑微血管内皮细胞在体有明显的表达。结论:脑微血管内皮细胞存在PAR-1,ICH后凝血酶激活PAR-1不仅是ICH后脑水肿产生的始动因素,而且参与了脑水肿的发展过程。     

Is there a familial link between Down's syndrome and neural tube defects? Population and familial survey

Objective To verify whether Down''s syndrome and neural tube defects arise more often in the same family than expected by chance.Design Population and familial survey.Setting Network of maternity hospitals in the Latin American collaborative study of congenital malformations (ECLAMC) in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Paraguay, Peru, Uruguay, and Venezuela between 1982 and 2000.Probands 2421 cases of neural tube defects, 952 of hydrocephalus, and 3095 of Down''s syndrome registered from a total of 1 583 838 live births and stillbirths.Main outcome measures Observed number of cases of Down''s syndrome among siblings of probands with a neural tube defect or hydrocephalus and number expected on the basis of maternal age; observed number of cases of neural tube defects or hydrocephalus among siblings of probands with Down''s syndrome and number expected according to the prevalence in the same population.Results Five cases of Down''s syndrome occurred among 5404 pregnancies previous to a case of neural tube defect or hydrocephalus, compared with 5.13 expected after adjustment by maternal age. Twelve cases of neural tube defect or hydrocephalus occurred among 8066 pregnancies previous to a case of Down''s syndrome, compared with 17.18 expected on the basis of the birth prevalence for neural tube defects plus hydrocephalus in the same population.Conclusion No association occurred between families at risk of neural tube defects and those at risk of Down''s syndrome.     

Disruption of Wave-associated Rac GTPase-activating Protein (Wrp) Leads to Abnormal Adult Neural Progenitor Migration Associated with Hydrocephalus

Hydrocephalus is the most common developmental disability and leading cause of brain surgery for children. Current treatments are limited to surgical intervention, as the factors that contribute to the initiation of hydrocephalus are poorly understood. Here, we describe the development of obstructive hydrocephalus in mice that are null for Wrp (Srgap3). Wrp is highly expressed in the ventricular stem cell niche, and it is a gene required for cytoskeletal organization and is associated with syndromic and psychiatric disorders in humans. During the postnatal period of progenitor cell expansion and ventricular wall remodeling, loss of Wrp results in the abnormal migration of lineage-tagged cells from the ventricular region into the corpus callosum. Within this region, mutant progenitors appear to give rise to abnormal astroglial cells and induce periventricular lesions and hemorrhage that leads to cerebral aqueductal occlusion. These results indicate that periventricular abnormalities arising from abnormal migration from the ventricular niche can be an initiating cause of noncommunicating hydrocephalus.     

Congenital hydrocephalus caused by exposure to low level X-radiation at early gestational stage in mice.

Hydrocephalus is a severe and often lethal birth defect in humans resulting from excess accumulation off cerebrospinal fluid (CSF) in the cranial vault, accompanied by enlargement of the head, prominence of the forehead and atrophy of the brain. A wide variety of teratogenic procedures have been used to obtain congenital hydrocephalus in laboratory animals. Radiation, infections, trypan blue, hypervitaminosis A, salisylates and nutritional deficiencies were considered as the teratogens. Several investigators induced congenital hydrocephalus following irradiation of pregnant animals. The purpose off this study is to elucidate the pathogenesis off congenital hydrocephalus induced by X-irradiation in mice. Since the sensitive period for malformations produced by X-radiation in mice ranges from gestational day 7 (G7) to Gl3.     

Tricarboxylic Acid Cycle Activity Measured by <Superscript>13</Superscript>C Magnetic Resonance Spectroscopy in Rats Subjected to the Kaolin Model of Obstructed Hydrocephalus

Evaluating early changes in cerebral metabolism in hydrocephalus can help in the decision making and the timing of surgical intervention. This study was aimed at examining the tricarboxylic acid (TCA) cycle rate and ¹³C label incorporation into neurotransmitter amino acids and other compounds 2 weeks after rats were subjected to kaolin-induced progressive hydrocephalus. In vivo and ex vivo magnetic resonance spectroscopy (MRS), combined with the infusion of [1,6-¹³C]glucose, was used to monitor the time courses of ¹³C label incorporation into the different carbon positions of glutamate in the forebrains of rats with hydrocephalus as well as in those of controls. Metabolic rates were determined by fitting the measured data into a one-compartment metabolic model. The TCA cycle rate was 1.3 ± 0.2 μmoles/gram/minute in the controls and 0.8 ± 0.4 μmoles/gram/minute in the acute hydrocephalus group, the exchange rate between α-ketoglutarate and glutamate was 4.1 ± 2.5 μmoles/gram/minute in the controls and 2.7 ± 2.6 μmoles/gram/minute in the hydrocephalus group calculated from in vivo MRS. There were no statistically significant differences between these rates. Hydrocephalus caused a decrease in the amounts of glutamate, alanine and taurine. In addition, the concentration of the neuronal marker N-acetyl aspartate was decreased. ¹³C Labelling of most amino acids derived from [1,6-¹³C]glucose was unchanged 2 weeks after hydrocephalus induction. The only indication of astrocyte impairment was the decreased ¹³C enrichment in glutamine C-2. This study shows that hydrocephalus causes subtle but significant alterations in neuronal metabolism already early in the course of the disease. These sub-lethal changes, however, if maintained and if ongoing might explain the delayed and programmed neuronal damage as seen in chronic hydrocephalus.     

Larsen syndrome associated with severe congenital hydrocephalus

Larsen syndrome associated with severe congenital hydrocephalus: Larsen syndrome (LS) is characterized by the association of flattened facies with a prominent forehead, a depressed nasal bridge and hypertelorism, dislocation of hips, elbows and knees, equinovarus or valgus deformities of the feet, long and tapering fingers, normal intelligence. Hydrocephalus has rarely been reported in association with LS. In this article, a newborn infant with the classical features of LS and severe congenital hydrocephalus is presented. Our purpose was to emphasize the importance of congenital hydrocephalus in infants with LS and to highlight the management of cases of LS associated with congenital hydrocephalus.     

VEGF: A potential target for hydrocephalus

Growth factors are primarily responsible for the genesis, differentiation and proliferation of cells and maintenance of tissues. Given the central role of growth factors in signaling between cells in health and in disease, it is understandable that disruption of growth factor-mediated molecular signaling can cause diverse phenotypic consequences including cancer and neurological conditions. This review will focus on the specific questions of enlarged cerebral ventricles and hydrocephalus. It is also well known that angiogenic factors, such as vascular endothelial growth factor (VEGF), affect tissue permeability through activation of receptors and adhesion molecules; hence, recent studies showing elevations of this factor in pediatric hydrocephalus led to the demonstration that VEGF can induce ventriculomegaly and altered ependyma when infused in animals. In this review, we discuss recent findings implicating the involvement of biochemical and biophysical factors that can induce a VEGF-mimicking effect in communicating hydrocephalus and pay particular attention to the role of the VEGF system as a potential pharmacological target in the treatment of some cases of hydrocephalus. The source of VEGF secretion in the cerebral ventricles, in periventricular regions and during pathologic events including hydrocephalus following hypoxia and hemorrhage is sought. The review is concluded with a summary of potential non-surgical treatments in preclinical studies suggesting several molecular targets including VEGF for hydrocephalus and related neurological disorders.     

Myosin IXa Regulates Epithelial Differentiation and Its Deficiency Results in Hydrocephalus

The ependymal multiciliated epithelium in the brain restricts the cerebrospinal fluid to the cerebral ventricles and regulates its flow. We report here that mice deficient for myosin IXa (Myo9a), an actin-dependent motor molecule with a Rho GTPase–activating (GAP) domain, develop severe hydrocephalus with stenosis and closure of the ventral caudal 3rd ventricle and the aqueduct. Myo9a is expressed in maturing ependymal epithelial cells, and its absence leads to impaired maturation of ependymal cells. The Myo9a deficiency further resulted in a distorted ependyma due to irregular epithelial cell morphology and altered organization of intercellular junctions. Ependymal cells occasionally delaminated, forming multilayered structures that bridged the CSF-filled ventricular space. Hydrocephalus formation could be significantly attenuated by the inhibition of the Rho-effector Rho-kinase (ROCK). Administration of ROCK-inhibitor restored maturation of ependymal cells, but not the morphological distortions of the ependyma. Similarly, down-regulation of Myo9a by siRNA in Caco-2 adenocarcinoma cells increased Rho-signaling and induced alterations in differentiation, cell morphology, junction assembly, junctional signaling, and gene expression. Our results demonstrate that Myo9a is a critical regulator of Rho-dependent and -independent signaling mechanisms that guide epithelial differentiation. Moreover, Rho-kinases may represent a new target for therapeutic intervention in some forms of hydrocephalus.     

Craniofacial configuration and postcranial development of a hydrocephalic child (ca. 2500 B.C.-500 A.D.): with a review of cases and comment on diagnostic criteria

Hydrocephalus is a severe disorder of the central nervous system characterized by absorption blockage of the cerebral spinal fluid (CSF). The archaeological record of the condition ranges in time from 10,000 B.C. to 1670 A.D. and consists of 30 possible cases worldwide. A review of this material reveals that diagnostic criteria which fully delineate the condition have not been established. Previously, no attempt has been made to differentiate the two major categories of hydrocephalus and their subgroupings, or to identify other conditions which might result in similar morphologies. A partial child's skeleton from the Middle Period (ca. 2500 B.C. to 500 A.D.) of Central California Prehistory is described in light of an extensive clinical literature. Examination of this individual reveals a unique craniofacial configuration and malformed postcrania. Bony criteria for a differential diagnosis of hydrocephalus are established and applied to this individual. Based on these criteria, the individual is diagnosed as having a chronic form of noncommunicating hydrocephalus. Blockage of the CSF pathway most likely occurred in the aqueduct of Sylvius with a partial occlusion of the foramen of Monro or a frontal cyst. In addition, femoral development is suggestive of partial paralysis.     

Multigenic factors associated with a hydrocephalus-like phenotype found in inter-subspecific consomic mouse strains

Hydrocephalus is a significant clinical condition in humans and is known to be a multifactorial neurologic disorder. It has been thought that genetic factors are closely involved in the etiology of congenital hydrocephalus, but further investigation is required to elucidate the genetic architecture of hydrocephalus. By analyzing breeding records of a panel of inter-subspecific consomic mouse strains, we found that consomic strains with MSM/Ms (MSM) chromosomes 4, 5, 7, 11, 15, and 17 showed a significantly higher incidence of hydrocephalus, whereas both parental strains, MSM and C57BL/6J (B6), rarely showed this abnormality. Further analysis of the consomic Chr 17 strain revealed that apparently normal individuals of this strain also exhibited increased brain ventricle size compared to B6 and had larger individual variation of ventricle size within the strain. Thus, we concluded that hydrocephalus is an extreme phenotype of individual ventricle size variation. We then established and analyzed several subconsomic strains of Chr 17 to identify genetic factors related to hydrocephalus-like phenotype and successfully mapped one genetic locus around the proximal region of Chr 17.     

Chlamydomonas reinhardtii hydin is a central pair protein required for flagellar motility

Mutations in Hydin cause hydrocephalus in mice, and HYDIN is a strong candidate for causing hydrocephalus in humans. The gene is conserved in ciliated species, including Chlamydomonas reinhardtii. An antibody raised against C. reinhardtii hydin was specific for an approximately 540-kD flagellar protein that is missing from axonemes of strains that lack the central pair (CP). The antibody specifically decorated the C2 microtubule of the CP apparatus. An 80% knock down of hydin resulted in short flagella lacking the C2b projection of the C2 microtubule; the flagella were arrested at the switch points between the effective and recovery strokes. Biochemical analyses revealed that hydin interacts with the CP proteins CPC1 and kinesin-like protein 1 (KLP1). In conclusion, C. reinhardtii hydin is a CP protein required for flagellar motility and probably involved in the CP-radial spoke control pathway that regulates dynein arm activity. Hydrocephalus caused by mutations in hydin likely involves the malfunctioning of cilia because of a defect in the CP.