小胶质与早产儿脑白质损伤的研究进展

脑室周围白质软化是早产儿最常见的脑损伤形式,常导致痉挛性脑瘫、认知及行为学异常等后遗症.小胶质是脑内的主要免疫应答细胞,在脑内防御反应及脑损伤的平衡机制中起重要作用.在其活化的早期,适当抑制小胶质的活化反应,能减少不必要的细胞毒性作用和病理损害.     

早产儿脑白质损伤的发病机制

早产儿脑白质损伤可造成神经系统发育障碍 ,其中包括永久性伤残 ,即脑性瘫痪。近年来关于早产儿脑白质损伤发病机制的研究有了新的进展 ,众多研究结果表明缺氧缺血和宫内感染是导致早产儿脑白质损伤的主要病因。该文主要综述了早产儿脑白质损伤的定义、病因、病理特点及发病机制的研究进展     

早产儿脑白质损伤的影像学诊断进展

早产儿脑白质损伤（white matter damage,WMD）,指24～35周出生的早产未熟儿由血管损伤和炎症反应而致的大脑白质病变,是早产儿最常见的脑损伤形式。19世纪中叶Parrot和Virchow等首先记载了本症,1962年Banker和Larroche又对本症做了详细报道,确定了PVL的概念。该病是导致早产儿伤残的重要原因。特别是脑室周围白质软化,[第一段]     

Circulating interferon-gamma and white matter brain damage in preterm infants

The fetal inflammatory response has been suggested as causal in neonatal morbidity. Serial levels of circulating cytokines were evaluated in 74 infants with a mean gestational age (GA) of 27.1 wk. Pro-inflammatory [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1 beta, IL-2, IL-6, IL-8, IL-12] [corrected] and modulatory (IL-4, IL-10) cytokines were analyzed from cord blood, and at 6, 24 [corrected] and 72 h postnatal age. Measure of cytokine burden over time was assessed by calculating the area under curve (AUC) for analyzed levels (0-72 h). Premature rupture of membranes (PROM) was associated with higher levels of IL-2 at birth and at 6 h, of IFN-gamma at 6 and 24 h postnatal age and of TNF-alpha at 6 and 24 h. Levels of IFN-gamma at 6, 24, and 72 h were increased in infants developing white matter brain damage (WMD) compared with those without WMD. Infants with arterial hypotension requiring dopamine treatment had an increase in IL-6 with a peak at 6 h of age. Severe intraventricular hemorrhage (IVH) was associated with increase in AUC [(IL-6) and (IL-8), odds ratio (OR) 2.8 and 13.2 respectively], whereas white matter brain damage (WMD) [corrected] was associated with increase in AUC (IFN-gamma; OR, 26.0) [corrected] A fetal immune response with increased postnatal levels of IFN-gamma was associated with development of WMD. PROM was associated with a T-helper 1 cytokine response with increased levels of IFN-gamma. Type of inflammatory response appears of importance for subsequent morbidity.     

Punctate white matter lesions of preterm infants: Risk factor analysis

AimPunctate white matter lesions (PWML) are frequently detected in preterm infants undergoing brain MRI at term equivalent age (TEA). The aims of this study were to assess prevalence of PWML and to identify risk factors for PWML in VLBW infants.MethodsBrain MRI scans obtained at TEA and clinical charts of a consecutive sample of very low birth weight (VLBW) infants admitted to Gaslini Children's Hospital NICU between 2012 and 2016 were retrospectively analyzed. MRI protocol included Susceptibility Weighted Imaging (SWI) sequence in order to identify hemosiderin depositions as a result of previous microbleeds. PWML were classified according to their number (≤6 lesions and >6 lesions) and signal characteristics (SWI+ lesions and SWI− lesions). Univariate and multivariable analysis were performed in order to identify risk factors for PWML (as a whole) and for each subgroup of PWML.Results321 VLBW infants were included. PWML were identified in 61 subjects (19%), 26 of whom (8% of the study population) had more than 6 lesions. Risk factors for PWML (as a whole) were higher birth weight (OR = 1.001; p = 0.04) and absent or incomplete antenatal steroid course (OR = 2.13; p = 0.02). Risk factors for >6 PWML were need for intubation (OR = 11.9; p = 0.003) and higher Apgar score at 5 min (OR = 1.8; p = 0.02). Presence of GMH-IVH was the only identified risk factor for SWI + lesions.ConclusionsOur results confirm the high prevalence of PWML among VLBW infants. Differentiation between SWI+ and SWI− lesions is crucial as they have different risk factors and may likely represent two different entities.     

线粒体功能障碍与早产儿脑白质损伤的研究进展

早产儿脑白质损伤病因复杂,可导致长期的神经认知行为缺陷,目前尚无特效的治疗手段。越来越多的研究表明,线粒体功能障碍在早产儿脑白质损伤发病过程中起重要作用,可能是脑白质发育障碍的常见亚细胞机制,涉及氧化应激、ATP合成减少、钙稳态失衡。文章将对线粒体在脑神经发育过程中的作用和造成其功能障碍的机制作一综述,希望能够通过保护线粒体功能对早产儿脑白质损伤进行及早干预,为改善存活早产儿神经发育结局提供参考。     

Effects of inspiratory resistive loading on chest wall motion and ventilation: differences between preterm and full-term infants.

The ability to maintain effective tidal volume and minute ventilation during resistive loaded breathing depends on both adequate central neural respiratory output response and respiratory system mechanical properties such as respiratory muscle strength and chest wall stability. We hypothesized that chest wall instability limits the ability of the preterm (PT) infant to respond to inspiratory resistive loading (IRL) compared with full-term (FT) infants. To test this hypothesis, we subjected eight FT and 10 PT infants to IRL with loads of 1.3, 2, and 6 times intrinsic lung resistance and measured steady state tidal volume (VT), minute ventilation (VE), and chest wall motion. Thoracoabdominal asynchrony was measured by respiratory inductive plethysmography and quantitated by measuring the phase angle, theta, between rib cage and abdominal motion (0 degrees = synchronous motion, 180 degrees = paradoxic motion). At baseline, VT/kg (mL/kg, mean +/- SEM) was similar between PT (7.0 +/- 0.7) and FT (7.5 +/- 0.5) infants. VE/kg (mL/min/kg) was greater in PT (545 +/- 50) than in FT (385 +/- 33) infants (p < 0.05) as a result of increased respiratory frequency in the former. PT infants demonstrated significantly greater chest wall asynchrony (theta = 38 +/- 9 degrees) than FT infants (theta = 9 +/- 3 degrees) (p < 0.01). With the highest resistive loads, VT decreased significantly in the PT but not the FT infants. Furthermore, during IRL, VE decreased to 417 +/- 50 mL/min/kg (p < 0.05) and theta increased to 56 +/- 7 (p < 0.05) in the PT infants, whereas no significant change in either value was observed in the FT group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of antenatal growth on brain white matter maturation in preterm infants at term using tract-based spatial statistics

Background

White matter maturation of infants can be studied using diffusion tensor imaging (DTI). DTI of the white matter of the infant brain provides the best available clinical measures of brain tissue organisation and integrity.

Objective

The purpose of this study was to compare white matter maturation between preterm infants born small for gestational age (SGA) and preterms with weight appropriate for gestational age (AGA) at birth.

Materials and methods

A total of 36 preterm infants were enrolled in the study (SGA, n?=?9). A rater-independent method called tract-based spatial statistics (TBSS) was used to assess white matter maturation.

Results

When measured by TBSS, the AGA infants showed higher fractional anisotrophy values in several white matter tracts than the SGA infants. Areas with significant differences included anterior thalamic radiation, corticospinal tract, forceps major and minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus, and superior longitudinal fasciculus (temporal part). No significant difference was found for mean diffusivity.

Conclusion

As an objective and user-independent method, TBSS confirmed that preterm infants with impaired antenatal growth have impaired white matter maturation compared to preterm infants with normal antenatal growth. The differences were mainly detected in radiations that are myelinated first.     

磁敏感加权成像在早产儿伴脑室旁白质损伤中的应用研究

目的脑室旁白质损伤是早产儿围生期窒息后常见的脑损伤类型之一,其MRI表现具有特征性,但常规序列难以区分病灶内是否合并出血,而出血与否可能影响治疗和预后。该研究应用磁敏感加权成像(SWAN)来检测存在白质损伤的早产儿脑内的出血性病变。方法对临床怀疑围生期窒息后脑损伤的75例早产儿行头颅GE HDx Twin Speed 3.0T MRI检查,扫描序列包括T1FLAIR、T2FLAIR、DWI和SWAN。结果44例(58.7%)早产儿存在脑室旁白质损伤,其中4例(9.1%)存在出血性白质损伤。在这4例中有3例合并生发基质出血-脑室内出血;4例合并小脑出血;1例合并蛛网膜下隙出血。结论脑室旁白质损伤中绝大多数为非出血性损伤,当伴有生发基质出血或脑室内出血时,脑室周围白质损伤病灶中常存在出血。     

Snsceptibility-weighted imaging findings in periventricular white matter injury in preterm infants

目的 脑室旁白质损伤是早产儿围生期窒息后常见的脑损伤类型之一,其MRI表现具有特征性,但常规序列难以区分病灶内是否合并出血,而出血与否可能影响治疗和预后.该研究应用磁敏感加权成像( SWAN)来检测存在白质损伤的早产儿脑内的出血性病变.方法 对临床怀疑围生期窒息后脑损伤的75例早产儿行头颅GE HDx Twin Speed 3.0T MRI检查,扫描序列包括T1FLAIR、T2FLAIR、DWI和SWAN.结果 44例(58.7％)早产儿存在脑室旁白质损伤,其中4例(9.1％)存在出血性白质损伤.在这4例中有3例合并生发基质出血-脑室内出血;4例合并小脑出血;1例合并蛛网膜下隙出血.结论 脑室旁白质损伤中绝大多数为非出血性损伤,当伴有生发基质出血或脑室内出血时,脑室周围白质损伤病灶中常存在出血.     

Sugar absorption in healthy preterm and full-term infants

We have studied carbohydrate absorption in 40 healthy term infants and 10 preterm neonates (31-35 weeks gestation) by respiratory H2, fecal pH, and chromatographic analysis of stools. Sequential studies of H2 excretion (24-h collection) in response to breast feeding were carried out in premature infants during the first 8 weeks of life. Five expired H2 during the first 2 weeks, and two continued to do so in the 3rd to 4th weeks. Breath H2 excretion fell below 10 ppm by 8 weeks and was not related to feeding or sleep. In term neonates, the frequency of incomplete carbohydrate absorption (4-h test) at the end of the first week was 36% for 14 breast-fed, 42% for 12 formula-fed, and 64% for 14 mixed-fed neonates (not significant differences). There were no significant differences between the absorbing and malabsorbing subjects in fecal pH. Chromatographic analysis showed only small quantities of sugars. In summary, incomplete carbohydrate absorption occurred in a high percentage of the newborns studied; the 24-h test evaluated better than the 4-h test; and negative breath H2 excretion indicated development of the capacity of the small intestine to hydrolyze carbohydrates. In the majority of the preterm malabsorbing babies, completely functional lactase occurs within the first month of life. The growth modulators in human milk may increase the rate of maturing of the small intestine.     

Neuromotor development of preterm and full-term infants

The Neuromotor Behavioral Inventory (NBI), a 16-category measure of muscle tone, developmental motor abilities, quality of movement, neurological reflexes and reactions, and neuromotor outcome was used with 38 infants divided into three groups: healthy preterm (HPT), sick preterm (SPT), and healthy full-term (HFT) infants. Infants were tested at five time points: 40 weeks postconception (newborn) and 3, 6, 9 and 12 months of age post-term. The intent of the study was two-fold: to determine whether there are developmental differences among the groups of infants and whether the differences persist during the first year of life. Results indicate that HFT and HPT infants score higher than SPT infants in the neuromotor categories of: muscle tone, upper extremity development, head control, and neuromotor outcome rating. HFT infants scored higher than both preterm groups in: trunk rotation, reaction to movement, visual and auditory attention, and fixing. Differences persisted among the groups during the first year of life in the following: the developmental motor ability of trunk rotation, fixing, adaptability, and the neuromotor outcome rating. It appears that neonatal health status is a contributing factor to infant neuromotor development, particularly in the quality of movement reactions.     

早产儿脑室周围强回声区分度与脑室周围白质囊性变的关系

目的：了解早产儿脑室周围强回声区（PVE）分度与脑室周围白质囊性变发生率及囊性变出现时间的关系。方法：对2005年2月至2008年5月间该院新生儿重症监护室住院超声诊断为PVE的120例早产儿（平均胎龄为32周,平均出生体重2 230 g）进行回顾性单元分析研究。结果：① 诊断为PVEⅠ度52例（43％）,PVEⅡ度42例（35％）,PVEⅢ度26例（22％）,PVE分度与出生体重密切相关,与胎龄无关。②120例早产儿脑白质囊性变发生率24％(29/120),PVEⅢ度囊性变发生率65％,Ⅱ度囊性变发生率21％,PVEⅢ度囊性变发生率明显高于PVEⅡ度。③囊性变出现的时间各不相同,PVEⅢ度组囊性变出现的时间明显早于PVEⅡ度组。结论：PVE分度与脑室周围白质囊性变出现的时间及囊性变发生率密切相关,因此对不同程度的PVE动态监测囊性变有不同的侧重点。［中国当代儿科杂志,2009,11（2）：104-106］     

Limitations of ultrasonography for diagnosing white matter damage in preterm infants

OBJECTIVES: To compare the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in diagnosing white matter abnormalities in preterm infants and to determine the specific indications for MRI. DESIGN: Prospective cohort study. SETTING: A neonatal intensive care unit in France. PATIENTS: All preterm infants (相似文献   

早产儿微小型脑白质损伤的MRI-DTI评价

目的 应用磁共振弥散张量成像(DTI)对不同程度的微小型脑白质损伤(CWMD)进行评价, 探讨DTI 在早产儿CWMD 中的应用价值。方法 选取2011 年11 月至2012 年4 月住院治疗的31 例早产儿, 分为局灶性CWMD 组11 例, 广泛性CWMD 组10 例, 同时正常对照组10 例, 比较三组患儿侧脑室旁的表观弥散系数(ADC)值及各向异性(FA)值, 应用Pearson 系数检验ADC 值及FA 值变化的相关性, 同时观察三组患儿的彩色FA 图。结果 局灶性CWMD 组及广泛性CWMD 组的ADC 值均高于正常组, 差异有统计学意义。局灶性CWMD 组及广泛性CWMD 组FA 值均低于正常组, 广泛性CWMD 组FA 值低于局灶性CWMD 组, 差异均有统计学意义。经过后处理的FA 彩图提示侧脑室周围白质区域的FA 值按正常组、局灶CWMD 组及广泛CWMD 组顺序依次减低。结论 弥散张量成像技术可定量评估微小型CWMD 程度。在CWMD 评价方面, FA 值比ADC 值可能更加准确。     

MRI和DTI评价早产儿脑白质髓鞘发育

目的 应用磁共振(MRI)、磁共振弥散张量成像(DTI)研究早产儿脑白质髓鞘发育的特点。方法 胎龄≤32周、出生体重<1 500 g的31例早产儿根据头部MRI检查分为早产脑损伤组(12例)和早产无脑损伤组(19例)。选取24例足月儿作为对照组。均于胎龄或纠正胎龄37~40周之间完成头部MRI及DTI检查。测定3组相同感兴趣区的部分各向异性参数(FA)和表观扩散系数(ADC)。结果 早产脑损伤组内囊后肢FA值小于早产无脑损伤组和足月对照组 (P < 0.05);早产脑损伤组和早产无脑损伤组的额叶白质和豆状核的FA值小于足月对照组 (P < 0.05);3组间枕叶白质的FA值差异无显著性 (P > 0.05)。早产脑损伤组和早产无脑损伤组内囊后肢、豆状核、枕叶白质、额叶白质的ADC值高于足月对照组 (P < 0.05)。结论 早产儿脑损伤容易出现内囊后肢深部脑白质髓鞘化障碍或延迟。早产儿至纠正胎龄足月时,无论有无脑损伤,脑周围白质及灰质成熟度均低于足月儿。     

早产儿缺氧缺血性脑白质损伤的神经病理学

近年来,随着产科和新生儿重症监护技术的不断提高,早产儿存活率增加,脑损伤的发病率亦呈逐年增加趋势.根据神经病理学分类 ,早产儿脑损伤可分为:     

早产儿脑室旁白质损伤发病机制的研究进展

脑室旁白质损伤是早产儿特征性脑损伤,也是早产儿最重要的脑病类型之一。其病理变化主要包括脑白质的凝固性坏死、少突胶质细胞损伤、髓鞘损害、轴突损伤以及坏死部位出现反应性胶质化和小胶质细胞浸润等,这些病变与新生儿期后的神经系统后遗症密切相关。早产儿脑室旁白质软化的发病机制主要是与脑血管发育未成熟和少突胶质细胞前体细胞损伤易感性有关。本文通过文献复习对早产儿脑室旁白质损伤发病机制的研究进展进行概述,为临床预防和诊治提供理论依据。     

Diffusion tensor imaging in preterm infants with punctate white matter lesions

Our aim was to compare white matter (WM) microstructure in preterm infants with and without punctate WM lesions on MRI using tract-based spatial statistics (TBSS) and probabilistic tractography. We studied 23 preterm infants with punctate lesions, median GA at birth 30 (25-35) wk, and 23 GA- and sex-matched preterm controls. TBSS and tractography were performed to assess differences in fractional anisotropy (FA) between the two groups at term equivalent age. The impact of lesion load was assessed by performing linear regression analysis of the number of lesions on term MRI versus FA in the corticospinal tracts in the punctate lesions group. FA values were significantly lower in the posterior limb of the internal capsule, cerebral peduncles, decussation of the superior cerebellar peduncles, superior cerebellar peduncles, and pontine crossing tract in the punctate lesions group. There was a significant negative correlation between lesion load at term and FA in the corticospinal tracts (p = 0.03, adjusted r2 = 0.467). In conclusion, punctate lesions are associated with altered microstructure in the WM fibers of the corticospinal tract at term equivalent age.