Clinical associations and time of onset of cerebral white matter damage in very preterm babies.

Neuropathological examinations were carried out at necropsy on 83 very pre-term babies who died during their first hospital admission. Forty seven (57%) babies had evidence of cerebral damage-39 with ischaemic white matter damage. The time of onset of ischaemic lesions was thought to be prenatal in 12 cases (31%) and postnatal in a further 12 (31%). The exact timing of damage could not be determined in 15 (38%) cases. Maternal and neonatal case notes were reviewed to ascertain clinical associations of ischaemic white matter damage. There were no clear associations between adverse clinical factors and prenatal ischaemic white matter damage. In contrast, pre-eclampsia, intrauterine growth retardation, and delivery without labour were associated with postnatal damage as were neonatal sepsis, necrotising enterocolitis, and seizures. The absence of a clear association between the timing of adverse clinical factors and the timing of ischaemic cerebral damage suggests that cerebral damage in very preterm babies may result from a sequence of events rather than one specific insult.     

Pathogenesis of cerebral white matter injury of prematurity

Cerebral white matter injury, characterised by loss of premyelinating oligodendrocytes (pre-OLs), is the most common form of injury to the preterm brain and is associated with a high risk of neurodevelopmental impairment. The unique cerebrovascular anatomy and physiology of the premature baby underlies the exquisite sensitivity of white matter to the abnormal milieu of preterm extrauterine life, in particular ischaemia and inflammation. These two upstream mechanisms can coexist and amplify their effects, leading to activation of two principal downstream mechanisms: excitotoxicity and free radical attack. Upstream mechanisms trigger generation of reactive oxygen and nitrogen species. The pre-OL is intrinsically vulnerable to free radical attack due to immaturity of antioxidant enzyme systems and iron accumulation. Ischaemia and inflammation trigger glutamate receptor-mediated injury leading to maturation-dependent cell death and loss of cellular processes. This review looks at recent evidence for pathogenetic mechanisms in white matter injury with emphasis on targets for prevention and treatment of injury.     

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     

Clinical characteristics of children with cerebral white matter abnormalities.

The rapidly expanding use of magnetic resonance imaging (MRI) in children with neurological impairments of unknown aetiology has revealed a large number of children with abnormalities of the cerebral white matter, some with leukodystrophy-like white matter abnormalities on MRI, but non-progressive in clinical presentation and course. The aim of this study was to investigate the clinical and neuroradiological characteristics of 26 children with white matter abnormalities of unknown origin and to find diagnostic clues or indicators of progressive versus nonprogressive disease. The typical child with white matter abnormalities was characterized by onset of symptoms within the first year of life, most often presenting as general developmental delay and hypotonia. Later-appearing signs were spasticity and ataxia and as a rule severe learning and motor disabilities. Serious ophthalmological signs were frequently seen. Perinatal adverse events were rare, infectious aetiologies not indicated but prenatal stigmata relatively common. The clinical course was progressive in 11 children and non-progressive in 15. Late onset presentation was associated with a progressive course whereas prenatal stigmata and asymmetrical white matter lesions only were found in children with a non-progressive disorder. The MRI showed three main patterns: a) a generalized increase of the T2 signal of the white matter in 12 children, b) a bilateral, symmetric but not generalized abnormality in nine and c) asymmetric, focal or multifocal pathology in five. Useful information as to clinical entities and course was obtained from the combined clinical and radiological assessment. A precise nosological diagnosis could be made in six cases. The study showed that white matter abnormalities in children constitute a heterogeneous group of rare and 'anonymous' conditions, motivating collaborative studies for further clarification of background and management.     

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动物模型

早产儿脑白质损伤是发生脑瘫的重要原因.合适的动物模型是研究脑白质损伤及脑瘫发生机制的关键.该文综述了不同类型实验动物的种类选择、特点,总结了近年来人们在体外实验的基础上,通过造成新生小鼠、大鼠、兔、羊、猪脑缺氧缺血,或通过颅内注射兴奋性氨基酸拟似物、细菌及脂多糖等途径,制作脑白质损伤模型的方法、结果及其如何对实验动物进行学习、记忆及运动发育评价,研究脑白质损伤与脑瘫的发生发展关系.     

Cerebral white matter injury in the newborn following Escherichia coli meningitis.

MR findings from six newborns with Escherichia coli (E. coli) meningitis are reported. Five of the six infants were infected with the K1 strain. All the infants displayed significant white matter injury on MR imaging. E. coli remains a serious cause of meningitis and MR imaging in this case series provides additional important information highlighting the vulnerability of the cerebral white matter in this condition in the newborn infant.     

先天性心脏病脑白质损伤研究进展

先天性心脏病(congenital heart disease,CHD)是最常见的出生缺陷疾病.近年来,随着心脏外科技术的显著提升,复杂性CHD新生儿和婴幼儿的生存率已经明显提高.然而,神经性后遗症仍然常见并且高达25％ ～55％.CHD术后大脑损伤最主要的是白质(white matter,WM)损伤.研究表明,以脑室周围WM软化病为特点的WM损伤常见于CHD婴幼儿尤其是心脏外科术后.既往人们认为这是由于术中体外循环和外科手术操作引起.然而,随着外科手术、医疗诊断技术的不断进步和基础研究的不断深入,人们发现CHD患儿WM损伤是术前、术中、术后多重因素综合作用的结果.这些患儿生长发育后期出现的运动障碍、注意力和学习等方面的缺陷给家庭和社会带来巨大经济负担,降低了人口素质.因此,探究CHD患儿WM损伤的原因、机制和防治方法成为近年CHD脑损伤研究热点,也可能成为未来进一步显著改善CHD患几神经发育损伤的重要研究方向.     

Depressive symptoms in adolescents: associations with white matter volume and marijuana use

BACKGROUND: Depressed mood has been associated with decreased white matter and reduced hippocampal volumes. However, the relationship between brain structure and mood may be unique among adolescents who use marijuana heavily. The goal of this study was to examine the relationship between white matter and hippocampal volumes and depressive symptoms among adolescent marijuana users and controls. METHODS: Data were collected from marijuana users (n = 16) and demographically similar controls (n = 16) aged 16-18. Extensive exclusionary criteria included psychiatric and neurologic disorders, including major depression. Substance use, mood, and anatomical measures were collected after 28 days of monitored abstinence. RESULTS: Marijuana (MJ) users demonstrated more depressive symptoms than controls (p < .05). MJ use (beta = .42, p < .005) and smaller white matter volume (beta = -.34, p < .03) each predicted higher levels of depressive symptoms on the Hamilton Depression Rating Scale. MJ use interacted with white matter volume (beta = -.55, p < .03) in predicting depression scores on the Beck Depression Inventory: among MJ users, but not controls, white matter volume was negatively associated with depressive symptoms. CONCLUSIONS: Marijuana use and white matter volume were additive and interactive in predicting depressive symptoms among adolescents. Subtle neurodevelopmental white matter abnormalities may disrupt the connections between areas involved in mood regulation.     

感染/炎症与早产儿脑白质损伤

感染/炎症是引起早产儿脑白质损伤的重要原因.其机制涉及炎症因子诱发的一系列级联反应,包括自由基损伤、兴奋性氨基酸释放、钙稳态失衡、细胞凋亡等.该文就它们在早产儿脑白质损伤中的机制及其治疗进展加以综述.     

感染/炎症与早产儿脑白质损伤

感染/炎症是引起早产儿脑白质损伤的重要原因.其机制涉及炎症因子诱发的一系列级联反应,包括自由基损伤、兴奋性氨基酸释放、钙稳态失衡、细胞凋亡等.该文就它们在早产儿脑白质损伤中的机制及其治疗进展加以综述.     

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:     

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.     

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。     

白质消融性白质脑病临床分析

目的分析白质消融性白质脑病的临床特点及诊断方法。方法对9例临床诊断为该病的患儿的临床及头颅影像学特点、实验室检查等进行分析,结合病例对该病进行综述介绍。结果（1）临床表现：9例中8例出现神经系统症状和体征,1例仅有MRI异常。发病时间为生后6个月-3岁;5例家族史阳性,病前智力运动发育多正常;多以运动症状起病,下肢为著。6例发病前或每遇病情加重前有呼吸道感染史,3例病前有轻微头部外伤史;到目前为止,有症状的7例呈进行性加重病程,其中4例同时有发作性加重现象。所有病例智力受损相对轻。7例头围正常,8例有上运动单元病变体征,4例有共济失调体征。3例双侧视神经萎缩。（2）头颅MRI：表现为双侧对称弥漫性深部白质长T1长T2信号,可累及皮层下白质,额、顶叶为主,Flair像为对称性白质高信号伴部分白质低信号甚至囊性变或大部分白质低信号仅存少量线状稍高信号,为此症特征性改变。（3）其他遗传性白质脑病相关酶学或生化检查均正常。结论以运动障碍起病、运动障碍重于智力障碍、神经影像学改变显著重于临床表现、MRI表现为双侧对称弥漫性深部白质长T1长T2病变伴早期出现白质消融征象是本症的临床特点,临床诊断还需除外其他遗传性及获得性脑白质病。找到相应基因的致病突变可最终确诊。     

Potential neuronal repair in cerebral white matter injury in the human neonate

Periventricular leukomalacia (PVL) in the premature infant represents the major substrate underlying cognitive deficits and cerebral palsy and is characterized as focal periventricular necrosis and diffuse gliosis in the immature cerebral white matter. We have recently shown a significant decrease in the density of neurons in PVL relative to controls throughout the white matter, including the subventricular, periventricular, and subcortical regions. These neurons are likely to be remnants of the subplate and/or GABAergic neurons in late migration to the cerebral cortex, both of which are important for proper cortical circuitry in development and throughout adulthood. Here, we tested the hypothesis that intrinsic repair occurs in PVL to attempt to compensate for the deficits in white matter neurons. By using doublecortin (DCX) immunopositivity as a marker of postmitotic migrating neurons, we found significantly increased densities (p < 0.05) of DCX-immunopositive cells in PVL cases (n = 9) compared with controls (n = 7) in the subventricular zone (their presumed site of origin), necrotic foci, and subcortical white matter in the perinatal time-window, i.e. 35-42 postconceptional weeks. These data provide the first evidence suggestive of an attempt at neuronal repair or regeneration in human neonatal white matter injury.     

脂多糖诱导小胶质细胞依赖的早产鼠脑白质损伤机制研究

目的:研究中枢神经系统小胶质细胞（MG）正常发育尤其是少突胶质细胞前体细胞（OPCs) 最易受损阶段的发育,探讨宫内感染早产鼠MG依赖的OPCs损伤机制。方法:①观察正常C57B/L鼠不同胎龄(孕10、15 d )和生后(0、5、10 d)MG和OPCs在脑白质的发育分布情况,明确两者在发育和分布上的关联。②建立脂多糖（LPS）宫内感染新生鼠模型（宫内分别接种LPS 5、10和20 μg·mL-1为感染A～C组）,以PBS溶液接种为对照组。以Tomato lectin作为静息状态MG标志,CD68作为活化MG的特殊抗体,O4+作为OPCs抗体,抗体浮片法进行免疫组化染色并计数分析。③ Western blot法检测各组脑室周围白质组织Toll样受体-4 (TLR-4)蛋白表达。④ 采用ELISA法检测各组MG活化后IL-2、TNF-α和SOD水平变化。结果:①MG在孕10 d胎鼠Tomato lectin表达低下,孕15 d胎鼠表达显著增高,MG主要分布在脑室周围白质区域,灰质皮质几乎不表达。出生后,脑室周围白质区域MG的表达有所下降,灰质皮质的表达逐渐增高。②感染A~C组CD68+细胞数量均显著增加,与对照组差异有统计学意义(P<0.01),但感染C组与B组CD68+细胞数量差异无统计学意义(P>0.05)。与对照组比较,感染A~C组均可见O4+细胞数量显著性下降(P<0.01),其中以感染C组下降最为明显。③对照组未检测到TLR-4蛋白表达, 感染A~C组均可见LPS剂量依赖的TLR-4蛋白表达增加,与对照组差异有统计学意义(P<0.05)。④随接种LPS剂量增大,IL-2和TNF-α水平较对照组呈显著增加趋势, SOD水平较对照组呈显著降低趋势。结论:新生鼠发育依赖的MG在脑白质受损区域过度表达,表明活化MG起到本底激活效应,是早产儿脑白质损伤的物质基础。