Prevalence of neonatal ultrasound brain lesions in premature infants with and without intrauterine growth restriction

AIM: To compare the prevalence of transient periventricular echodensities (TPE), periventricular leukomalacia (PVL) and haemorrhagic brain lesions (HBL) in singleton intrauterine growth-restricted (IUGR) infants and in those appropriate for gestational age (AGA). METHODS: Thirty-five IUGR and 35 AGA singleton infants born between 24- and 34-week gestational age were studied. The presence of TPE, PVL and HBL was assessed with ultrasound (US) at day 3 (US-I), 2 weeks (US-II) after delivery and at term-equivalent age (US-III). RESULTS: IUGR neonates had an increased prevalence of TPE at US-I (18/35 vs. 8/35, p= 0.02) and an increased prevalence of PVL at US-II (8/32 vs. 1/31, p = 0.03) and US-III (8/29 vs. 1/29, p = 0.02). No significant differences in the prevalence of HBL were found between the two groups. CONCLUSIONS: IUGR is associated with an increased prevalence of white matter damage on US brain scans in preterm neonates.     

Fetal stroke and cerebrovascular disease: Advances in understanding from lenticulostriate and venous imaging,alloimmune thrombocytopaenia and monochorionic twins

Fetal stroke is an important cause of cerebral palsy but is difficult to diagnose unless imaging is undertaken in pregnancies at risk because of known maternal or fetal disorders. Fetal ultrasound or magnetic resonance imaging may show haemorrhage or ischaemic lesions including multicystic encephalomalacia and focal porencephaly. Serial imaging has shown the development of malformations including schizencephaly and polymicrogyra after ischaemic and haemorrhagic stroke. Recognised causes of haemorrhagic fetal stroke include alloimmune and autoimmune thrombocytopaenia, maternal and fetal clotting disorders and trauma but these are relatively rare. It is likely that a significant proportion of periventricular and intraventricular haemorrhages are of venous origin. Recent evidence highlights the importance of arterial endothelial dysfunction, rather than thrombocytopaenia, in the intraparenchymal haemorrhage of alloimmune thrombocytopaenia. In the context of placental anastomoses, monochorionic diamniotic twins are at risk of twin twin transfusion syndrome (TTTS), or partial forms including Twin Oligohydramnios Polyhydramnios Sequence (TOPS), differences in estimated weight (selective Intrauterine growth Retardation; sIUGR), or in fetal haemoglobin (Twin Anaemia Polycythaemia Sequence; TAPS). There is a very wide range of ischaemic and haemorrhagic injury in a focal as well as a global distribution. Acute twin twin transfusion may account for intraventricular haemorrhage in recipients and periventricular leukomalacia in donors but there are additional risk factors for focal embolism and cerebrovascular disease. The recipient has circulatory overload, with effects on systemic and pulmonary circulations which probably lead to systemic and pulmonary hypertension and even right ventricular outflow tract obstruction as well as the polycythaemia which is a risk factor for thrombosis and vasculopathy. The donor is hypovolaemic and has a reticulocytosis in response to the anaemia while maternal hypertension and diabetes may influence stroke risk. Understanding of the mechanisms, including the role of vasculopathy, in well studied conditions such as alloimmune thrombocytopaenia and monochorionic diamniotic twinning may lead to reduction of the burden of antenatally sustained cerebral palsy.     

新生大鼠脑白质损害模型神经胶质细胞的凋亡及 MK2、Nogo-B的表达研究

目的观察2日龄(P2)新生大鼠脑白质损害(WMD)后神经胶质细胞凋亡及丝裂原活化蛋白激酶活化蛋白激酶2(MK2)、Nogo-B的变化;探讨神经胶质细胞凋亡与MK2、Nogo-B变化的时相关系。方法制备新生鼠WMD模型,分别于WMD后30 min、1 h、4 h、12 h、1 d、3 d、7 d、14 d及21 d处死大鼠,TUNEL法检测脑白质神经细胞凋亡,免疫组化(SP)法检测Nogo-B蛋白的表达,原位杂交(POD法)检测MK2 mRNA表达。结果WMD组大鼠凋亡指数在缺氧缺血4 h、12 h、1 d、3 d、7 d组与对照组相比,差异有统计学意义(P<0.05);WMD后1 h MK2mRNA在脑室周围白质及胼胝体区表达上调,并于损伤后3 d达到高峰。Nogo-B在WMD后12 h表达增加,3 d达高峰,在12 h、1 d、3 d、7 d的表达与对照组相比,差异有统计学意义(P<0.05)。结论MK2、Nogo-B在新生大鼠脑白质损害时表达增高,提示其参与了脑白质损害。     

早产儿脑室周围-脑室内出血预防的临床证据

目的 寻找与早产儿脑室周围-脑室内出血(PVH-IVH)预防相关的临床证据,并探讨其临床应用价值.方法 检索MEDLINE、EMBASE、Oxford围产新生儿组资料库和Cochrane图书馆关于PVH-IVH危险因素和预防相关的系统评价和随机(半随机)对照研究(randomised or quasi-randomised controlled trials,RCT),并进行分析.结果 产前母亲使用皮质激素、出生时延迟结扎脐带可显著降低早产儿PVH-IVH发生率,出生后预防性使用消炎痛可降低早产儿严重IVH的发生率,但对神经系统远期预后没有影响.结论 推荐产前母亲单次使用皮质激素预防早产儿PVH-IVH的发生,消炎痛和产前多次使用皮质激素尚待更多的前瞻性RCT来证实其安全性和有效性.     

未成熟脑白质缺血性损伤和谷氨酸异常信号传输

目的探讨缺血诱导谷氨酸异常信号传输对未成熟脑白质的损伤作用。方法分别制备2日龄新生大鼠少突胶质细胞(OL)前体氧糖剥夺(OGD)细胞模型和缺血型脑室周围白质软化(PVL)动物模型。于OGD后24小时,收集细胞及上清液,应用高效液相色谱仪测定OL前体胞外谷氨酸浓度,流式细胞仪检测胞内钙离子浓度以及OL前体凋亡率。新生大鼠于造模后第5天处死取脑,分别进行光镜下脑白质病理评估、免疫组化法检测髓鞘碱性蛋白(MBP)阳性成熟OL百分比以及电镜下脑白质髓鞘化评估。结果体外与无氧糖剥夺的正常组OL前体相比,OGD组OL前体胞外谷氨酸呈大量蓄积(P0.01),胞内钙离子浓度显著增加(P0.01),OL前体的凋亡率和坏死率亦明显增高(P0.01,P0.05)。体内与假手术(Sham)组正常新生大鼠相比,PVL组所有大鼠脑白质均显现轻度或重度的病理改变,脑白质内MBP阳性成熟OL明显减少,髓鞘亦形成不良,表现为髓鞘数目明显减少和髓鞘厚度明显变薄(P均0. 01)。结论未成熟脑白质具有与成熟脑白质相似的谷氨酸信号传输特点。缺血诱导未成熟脑白质内谷氨酸异常信号传输。     

胎盘评估早产儿脑损伤不良结局的研究进展

随着产科及新生儿重症监护技术的迅猛发展，具有极限生存活力的早产儿存活率逐年提高。但因神经系统发育不成熟，易受到各种高危因素的影响，致使脑损伤的发病率逐年上升，严重威胁早产儿的生长发育及身心健康。胎盘作为母体与胎儿连接的纽带，近年来已成为研究早产儿神经系统发育不良结局的重要器官。目前研究发现，与早产儿脑损伤有关的胎盘组织病理常伴有急性绒毛膜羊膜炎、胎盘灌注不良、绒毛膜血管病等改变；分子病理可表现为炎症因子释放增加、缺氧诱导因子过度表达与胎盘外泌体保护作用下调等变化；胎盘微小RNA（miRNAs）则可以随着宫内环境的变化而变化，反映出表观遗传调控在保护胎儿神经系统不受外来因素影响中的作用。本文从组织病理学、分子病理学及表观遗传学等方面综述早产儿胎盘的变化特点，及对神经系统发育影响的机制，以及检测早产儿胎盘对评估脑损伤不良结局的意义。     

Relationship between characteristics on magnetic resonance imaging and motor outcomes in children with cerebral palsy and white matter injury

In a population cohort of children with white matter injury (WMI) and cerebral palsy (CP), we aimed to describe the magnetic resonance imaging (MRI) characteristics, identify key structure–function relationships, and classify the severity of WMI in a clinically relevant way. Stratified on MRI laterality/symmetry, variables indicating the extent and location of cerebral abnormalities for 272 children with CP and WMI on chronic-phase MRI were related to gross motor function and motor topography using univariable and multivariable approaches. We found that symmetrical involvement, severe WM loss in the hemispheres and corpus callosum, and cerebellar involvement were the strongest predictors of poor gross motor function, but the final model explained only a small proportion of the variability. Bilateral, extensive WM loss was more likely to result in quadriplegia, whereas volume loss in the posterior-mid WM more frequently resulted in diplegia. The extent and location of MRI abnormalities differed according to laterality/symmetry; asymmetry was associated with less extensive hemispheric involvement than symmetrical WMI, and unilateral lesions were more focal and located more anteriorly. In summary, laterality/symmetry of WMI, possibly reflecting different pathogenic mechanisms, together with extent of WM loss and cerebellar abnormality predicted gross motor function in CP, but to a limited extent.     

Central catecholamine neurons and exposure to dichloromethane. Selective changes in amine levels and turnover in tel- and diencephalic DA and NA nerve terminal systems and in the secretion of anterior pituitary hormones in the male rat

Subacute exposure of male rats to various concentrations (70–1000 ppm) of dichloromethane (DCM) produces a selective reduction of dopamine (DA) levels without a change of DA turnover in certain types of forebrain DA nerve terminal systems. In the low concentration (70 ppm) a selective reduction of DA turnover was observed in the medial palisade zone (MPZ) of the median eminence. This chlorinated organic solvent also produced a discrete dose-dependent increase of noradrenaline (NA) turnover within the     

Reversal of the sexually dimorphic distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus by treatment with perinatal androgen

A small, discrete nucleus at the rostral end of the third ventricle, the anteroventral periventricular nucleus (AVPv), has been reported to be involved in the control of gonadotropin release. Since monoaminergic neurotransmitter systems have also been implicated in this function we used an indirect immunohistochemical approach to examine the distribution of 3 monoaminergic neurotransmitter systems in this nucleus. Sections through the AVPv of both colchicine and non-colchicine-treated adult male and female Sprague-Dawley rats were processed for immunohistofluorescence with antisera directed against tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), or serotonin (5-HT), and were subsequently counterstained with the fluorescent Nissl stain ethidium bromide. The distributions of TH-, DBH- and 5-HT-immunoreactive neural elements within the AVPv were evaluated and a comparison was made between males and females. In both sexes, few 5-HT-stained fibers were seen within the borders of the AVPv, in contrast to the relatively high 5-HT-stained fiber density of the surrounding region. A dramatic sexual dimorphism was found in the distribution of TH-immunoreactive fibers and cell bodies. Compared to males, the AVPv in the female contained 3-4 times as many TH-stained perikarya, and a 2- to 3-fold greater density of TH-stained fibers. A low to moderate density of DBH-immunoreactive fibers, and no DBH-stained cell bodies, were seen in the nucleus. A clear sex difference was not found in the density of DBH-stained fibers in the AVPv, indicating that the sexual dimorphism in TH-immunoreactive neural elements in this nucleus is due to a greater density of dopaminergic fibers and a greater number of dopaminergic cell bodies in the female. These results suggest that dopamine may participate in the control of gonadotropin secretion at the level of the AVPv.