White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain

Free radicals seem to be involved in the development of cerebral white matter damage after asphyxia in the premature infant. The immature brain may be at increased risk of free radical mediated injury, as particularly the preterm infant has a relative deficiency in brain antioxidants systems, such as superoxide dismutase and glutathione peroxidase. In vitro studies show that immature oligodendrocytes express an intrinsic vulnerability to reactive oxygen species and free radical scavengers are able to protect immature oligodendrocytes from injury. The aim of this study was to examine the formation of ascorbyl radicals as a marker of oxidative stress in the preterm brain in association with cerebral white matter injury after intrauterine asphyxia. Fetal sheep at 0.65 gestation were chronically instrumented with vascular catheters and an occluder cuff around the umbilical cord. A microdialysis probe was placed in the periventricular white matter. Fetal asphyxia was induced by occlusion of the umbilical cord for 25 min (n = 10). Microdialysis samples were collected for 72 h and analyzed for ascorbyl radicals using electron spin resonance. Five instrumented fetuses served as controls. Three days after the insult, fetal brains were examined for morphologic injury. Umbilical cord occlusion resulted in prolonged and marked increase in ascorbyl radical production in the brain in connection with white matter injury, with activation of microglia cells in periventricular white matter and axonal injury. These data suggest that reperfusion injury following asphyxia in the immature brain is associated with marked free radical production.     

Melatonin reduces inflammation and cell death in white matter in the mid-gestation fetal sheep following umbilical cord occlusion

The premature infant is at increased risk of cerebral white matter injury. Melatonin is neuroprotective in adult models of focal cerebral ischemia and attenuates ibotenate-induced white matter cysts in neonatal mice. Clinically, melatonin has been used to treat sleep disorders in children without major side effects. The aim of this study was to investigate the protective and anti-inflammatory effects of melatonin in the immature brain following intrauterine asphyxia. Fetal sheep at 90 d of gestation were subjected to umbilical cord occlusion. Melatonin (20 mg/kg, n = 9) or vehicle (n = 10) was administered IV to the fetus, starting 10 min after the start of reperfusion and continued for 6 h. Melatonin treatment resulted in a slower recovery of fetal blood pressure following umbilical cord occlusion, but without changes in fetal heart rate, acid base status or mortality. The production of 8-isoprostanes following umbilical cord occlusion was attenuated and there was a reduction in the number of activated microglia cells and TUNEL-positive cells in melatonin treated fetuses, suggesting a protective effect of melatonin. In conclusion, this study shows that melatonin attenuates cell death in the fetal brain in association with a reduced inflammatory response in the blood and the brain following intrauterine asphyxia in mid-gestation fetal sheep.     

双胎输血综合征胎儿和生后2天脑损伤的队列研究

目的：验证双胎输血综合征（TTTS）新生儿脑损伤起源于宫内还是宫外。方法：前瞻性队列研究设计,在同一医院以超声作为TTTS、颅内出血和脑室周围白质软化的诊断工具,纳入孕34周前分娩的接受双胎儿颅脑超声和生后2 d内新生儿颅脑超声检查的TTTS孕妇。排除双胎儿均宫内死亡和双胎之一严重结构异常或染色体异常。结果：47例TTTS孕妇的94例胎儿进入本文分析,孕妇中位年龄31 (18~46) 岁,TTTS诊断孕周16~28周,终止妊娠孕周28~33+5 周。QuinteroⅠ、Ⅱ、Ⅲ、Ⅳ和Ⅴ期分别为7、9、17、8和6例。Ⅴ期6例胎儿期死亡,6例存活胎儿均发生颅内出血合并脑白质软化。88例胎儿超声发现19例脑损伤（21.6%）,受血儿5例,供血儿14例,受血儿26.3% vs 供血儿 73.6%,差异有统计学意义（P＜0.05）。TTTS的Ⅲ~Ⅴ级脑损伤17例,Ⅰ~Ⅱ级2例,Ⅲ~Ⅴ级30.3% vs Ⅰ~Ⅱ6.2%,差异有统计学意义（P＜0.05）。孕19~28周接受羊水减量术治疗13/47例（27.7%）,均未在治疗后新发现脑损伤。88例均为早产儿,胎龄（30.5±4.5）周。受血儿体重（1 607±438）g,供血儿体重（1 257±403）g,生后24 h因新生儿窒息死亡4例。84例早产儿中头颅超声发现24例脑损伤（28.6%）,受血儿9例,供血儿15例,受血儿37.5% vs供血儿 62.5%,差异有统计学意义（P＜0.05）。颅内出血Ⅰ级5例,均为生后诊断且不合并脑白质软化。颅内出血Ⅱ级中,胎儿阶段11例,新生儿阶段增加了4例颅内出血Ⅱ级,其中1例合并脑白质软化,3例转为颅内出血Ⅲ级伴脑白质软化,无死亡。颅内出血Ⅲ级中,胎儿阶段5例均合并脑白质软化,新生儿阶段5例,3例由颅内出血Ⅱ级进展,死亡1例。颅内出血Ⅳ级中,胎儿阶段3例均合并脑白质软化,新生儿阶段2例均由颅内出血Ⅲ级进展,均死亡。结论：TTTS胎儿产前脑受损已出现,与早产共同造成脑损伤,以脑室出血、脑室白质软化为多见。对于所有存活儿都应该进行产前规范的超声监测及生后及时的新生儿头颅超声筛查。     

The production of hydroxyl radicals in the fetal lamb brain resulting from occlusion of the umbilical circulation and the transplacental effect of MCI-186 to inhibit hydroxyl radical production

The present study evaluated hydroxyl radical production in fetal lamb brain during and after umbilical cord occlusion and examined the effects of injecting MCI-186 (3-metyl-1-phenyl-2-pyrazolin-5-one; Edaravone), a hydroxyl radical scavenger, into the maternal circulation. In 11 chronically instrumented lambs, intermittent total umbilical cord occlusions 1 min out of every 3 min for 1 h and 10-min persistent total umbilical cord occlusion were performed with brain microdialysis using 5 mM of sodium salicylate. In the remaining four lambs, 60 mg of MCI-186 was administered into the maternal circulation from shortly before the end of 10-min persistent total umbilical cord occlusion. Concentrations of 2,3-dihydroxy-benzoic acid (2,3-DHBA), produced by hydroxyl radical reactions with sodium salicylate, were measured in perfusate by HPLC. Concentration of 2,3-DHBA in perfusate was 23.05 +/- 10.95 nM before umbilical cord occlusion. Levels of 2,3-DHBA tended to increase slightly during and after intermittent umbilical cord occlusion, and were significantly increased by the end of 10-min occlusion (40.06 +/- 21.36 nM) and after occlusion (93.74 +/- 29.17 nM). Infusion of MCI-186 suppressed 2,3-DHBA concentration to 29.35 +/- 14.95 nM after occlusion. Administration of MCI-186 into the maternal circulation reduces hydroxyl radical production induced by umbilical cord occlusion in the fetal lamb brain.     

脑室周围白质软化新生大鼠模型的创建及所伴随的白内障病变

目的：创建与人类早产儿脑室周围白质软化（periventricular leukomalacia，PVL）病理相似的可靠PVL动物模型，并探索本PVL模型所伴随的白内障病变及其形成机制。方法：新生大鼠分为PVL组和假手术对照组，通过双侧颈总动脉结扎和8％低氧下缺氧30 min，建立PVL动物模型。分别于术后1 d进行脑片TTC染色以观察脑梗死情况，术后2 d和21 d进行光镜下脑病理检查，以及术后21 d进行眼部裂隙灯检查和光镜下眼球病理检查。结果：脑片TTC染色显示PVL新生大鼠脑组织呈现大面积白色梗死区，其梗死体积达（53.45±33.90） mm3，梗死百分比为（24.98±15.44）％。光镜下病理研究证实，术后2 d的PVL新生大鼠脑室周围以及皮层下白质呈现囊性坏死和细胞凋亡，皮质神经元损伤轻微。术后21 d，其脑室周围以及皮质下白质可见多个囊性疏松坏死区域形成。相应日龄假手术组大鼠脑组织内则未观察到明显病理改变。术后21 d后，肉眼及裂隙灯下均观察到PVL组所有幼鼠双眼均呈现白内障，光镜下显示球后组织无明显病理改变。假手术组幼鼠眼部均正常。结论：通过对2日龄新生大鼠进行双侧颈总动脉结扎伴缺氧，成功创建了与人类早产儿PVL病理相似的PVL动物模型，效果肯定，重复性好。同时本建模方法也可引起白内障病变，可作为制作白内障动物模型的推荐方法之一。［中国当代儿科杂志，2007，9（3）：220-224］     

Analyses of factors contributing to vulnerability to antenatal periventricular leukomalacia induced by hemorrhagic hypotension in chronically instrumented fetal sheep.

Our purpose was to determine factors contributing to vulnerability to antenatal periventricular leukomalacia (PVL) induced by hemorrhagic hypotension in premature fetal sheep. Systemic hypotension was induced in 10 fetal sheep by acutely withdrawing 35% to 40% of the fetoplacental blood volume at 113 d gestation. Brains were processed for histologic analysis 6 d after the insult. Statistical comparisons of physiologic parameters between fetuses suffering from PVL (n = 5) and those without PVL (n = 5) were performed. Significant correlations were found between induction of PVL and fetal brain weight, changes in fetal mean blood pressure over time, base excess, oxygen content, hematocrit, and plasma arginine vasopressin (AVP) levels in fetal abdominal aortic blood. Brain developmental stage, the magnitude of induced systemic hypotension, and baseline blood oxygen content were important intrinsic factors in the induction of antenatal PVL by hemorrhagic hypotension in premature fetal sheep.     

Early detection of periventricular leukomalacia by diffusion-weighted magnetic resonance imaging techniques

Periventricular leukomalacia (PVL), the principal form of brain injury in the premature infant, is characterized by overt focal necrotic lesions in periventricular white matter and less prominent, more diffuse cerebral white matter injury. The early detection of the latter, diffuse component of PVL is not consistently possible with conventional brain imaging techniques. We demonstrate the early detection of the diffuse component of PVL by diffusion-weighted magnetic resonance imaging (DWI). In a premature infant with no definite cerebral abnormality detectable by cranial ultrasonography or conventional magnetic resonance imaging, DWI showed a striking bilateral decrease in water diffusion in cerebral white matter. The DWI abnormality (ie, decreased apparent diffusion coefficient) was similar to that observed with acute cerebral ischemic lesions in adults. At 10 weeks of age, conventional magnetic resonance imaging and ultrasonography showed striking changes consistent with PVL, including the presence of small cysts. The observations indicate the importance of DWI in the early identification of the diffuse component of PVL and also perhaps the role of ischemia in the pathogenesis of the lesion.     

Different responses of myocardial and cerebral blood flow to cord occlusion in exteriorized fetal sheep

Type and duration of fetal asphyxial insult affect the distribution of blood flow to the heart and brain. The purpose of this study was to describe dynamic and quantitative changes in regional myocardial and cerebral blood flow (CBF) during fetal asphyxia induced by total occlusion of the umbilical cord. Eleven exteriorized fetal sheep were subjected to total umbilical cord occlusion and five fetal sheep served as sham controls. Regional blood flow (BF) to the brain and heart was quantified using radioactive microspheres before and after 5 min of occlusion and finally when fetal mean arterial blood pressure had decreased below 25 mm Hg, 9.8 (0.8) [mean (SD)] min after occlusion. Right coronary arterial (RCA) blood flow velocity and carotid BF were registered continuously. Mean values of arterial pH and oxygen content (mL O(2)/100 mL) were 7.08 (0.11) and 4.4 (2.9) before cord occlusion and decreased to 6.83 (0.05) and 1.4 (0.9) at 5 min after occlusion (p < 0.01, respectively). Carotid BF was significantly below preocclusion values by 2.5 min (p < 0.05), whereas RCA velocity time integral per minute remained above preocclusion values for 9 min. CBF decreased from 316 (24) before cord occlusion to 156 (30) mL/min/100 g at 5 min (p < 0.01), whereas right myocardial BF was maintained at 792 (125) and 751 (183) mL/min/100 g, respectively. CBF decreased rapidly after total cord occlusion whereas myocardial BF increased and was maintained until shortly before cardiac arrest, suggesting the myocardium to be better preserved during this type of insult in already partially asphyxiated fetuses.     

经脑室神经干细胞移植对脑室周围白质软化新生大鼠的脑病理评估

目的：对经脑室植入神经干细胞（NSCs）的脑室周围白质软化（Periventricular leukolamacia，PVL）新生大鼠进行光镜下脑病理评估，探讨NSCs移植对治疗早产儿PVL的可行性。方法：采用E14胎鼠大脑皮层制备NSCs。2日龄新生大鼠随机分为PVL对照组（PVL组），PVL＋DMEM/F12培养基对照组（PVL＋DMEM/F12组），PVL＋神经干细胞（NSCs）移植组（PVL＋NSCs组），假手术对照组（Sham组），Sham＋DMEM／F12培养基对照组（Sham＋DMEM/F12组），Sham＋NSCs移植组（Sham＋NSCs组），每组18～21只。对2日龄PVL新生大鼠在建模后72 h进行经脑室NSCs移植，分别于移植后7，14，21 d进行光镜下脑病理评估。结果：随着移植后时间的增加，脑白质病变呈进一步改善。移植后21 d光镜下病理证实，未移植组脑白质呈轻度和重度病变各占50％，神经元病理评分为1.28±0.86。移植组则有30％白质完全正常，轻度和重度病变各占40％和30％，神经元病理评分为0.32±0.16，两组在脑白质病变程度以及神经元病理评分之间的差异均呈非常显著性意义（χ2＝10.7，P<0.01；F=29.664, P<0.01）。结论：经脑室外源性NSCs移植可明显改善脑白质的病理损伤。经脑室NSCs移植对早产儿PVL具有很大的治疗潜力，为今后成功防治早产儿这一最常见的脑损伤顽症提供了新的可行性途径。     

缺血启动未成熟大鼠脑白质内源性修复功能的研究

目的：探讨缺血启动未成熟脑白质的内源性修复机制。方法：5日龄 Sprague-Dawley 新生大鼠随机分为假手术（Sham）组和PVL组。分别于建模后7 d及21 d光镜、电镜下评估脑白质病变及髓鞘形成情况,免疫组化检测脑白质O4+少突胶质细胞（OL）前体,观察SVZ区祖细胞的激活、增殖、迁移和分化情况。结果：与Sham组比较,PVL组在建模后7 d和21 d光镜下脑白质病理均呈轻或重度病变;病理评分均明显增高;髓鞘形成数量明显减少,厚度变薄;免疫组化显示O4+OL前体明显减少。建模48 h后,PVL组SVZ 区 BrdU、NG2共阳性祖细胞明显增殖并向脑室周围迁移,至7 d达到高峰;从72 h开始,脑室周围出现呈BrdU、O4共阳性OL前体,至21 d,新生OL前体明显多于同时段Sham组。结论：缺血可启动新生大鼠脑白质的内源性修复机制,诱导SVZ 区胶质源性神经祖细胞激活、增殖、迁移至脑室周围和分化为OL前体。     

Cerebral white matter damage in the preterm infant: pathophysiology and risk factors

Based on clinical, epidemiologic, and experimental studies, the aetiology of white matter damage, specifically periventricular leukomalacia (PVL), is multifactorial and involves pre- and perinatal factors possibly including genetic factors, hypoxic-ischaemic insults, infection, excess cytokines, free radical production, increased excitatory amino acid release, and trophic factor deficiencies. The article summarizes research findings about the aetiology of white matter damage and cerebral palsy in preterm infants. The information is organized according to specific antecedents, for which we present epidemiological and neurobiological data. The most important prenatal factor appears to be intrauterine infection. We discuss the evidence supporting the hypothesis that the foetal inflammatory response contributes to neonatal brain injury and later developmental disability. We recently established an animal model of excitotoxic lesions in the developing mouse brain. Brain damage was induced by intra-cortical injections of ibotenate, a glutamatergic agonist. When administered on post-natal day 5 ibotenate induced the formation of white matter cysts. Our animal model could be used to further explore the mechanisms involved in the formation of PVL. Potentially preventive strategies will be discussed.     

经脑室神经干细胞移植治疗脑室周围白质软化新生大鼠电镜下脑病理评估

目的对经脑室植入神经干细胞(NSCs)的脑室周围白质软化(PVL)新生大鼠进行电镜下脑病理和髓鞘形成评估,探讨NSCs移植对治疗早产儿PVL的可行性,以及胶质细胞源性神经营养因子(GDNF)对NSCs治疗PVL的影响。方法采用颈部正中切开双侧颈总动脉结扎法制备PVL模型。采用孕14 d SD大鼠大脑皮质制备NSCs。2日龄新生大鼠随机分为PVL对照组(PVL组),PVL加NSCs移植组(PVL加NSCs组),PVL加NSCs移植及GDNF组(PVL加NSCs加GDNF组),假手术对照组(Sham组),Sham加NSCs移植组(Sham加NSCs组),以及Sham加NSCs移植及GDNF组(Sham加NSCs加GDNF组)。NSCs移植组将NSCs调整为5×107L-1,将2μL移植液以0.5μL/min注入侧脑室内。GDNF干预组以100μg/L GDNF加入NSCs移植液中注入侧脑室。对2日龄PVL新生大鼠在建模后72 h进行经脑室NSCs移植,分别于移植第21天行电镜下脑病理和髓鞘形成评估。结果移植第21天,电镜显示,PVL组可见部分神经元固缩变形,细胞器减少,罕见髓鞘形成。PVL加NSCs组皮质部位神经元形态基本正常,脑白质内髓鞘形成明显增加。PVL加NSCs加GDNF组皮质改善以及髓鞘形成增多情况较PVL加NSCs组则更为明显。假手术各组未见明显变化。结论经脑室NSCs移植对早产儿PVL具有很大的治疗潜力,GDNF可能具有增强NSCs的治疗作用。     

White matter damage in the preterm neonate

The most common form of brain injury in preterm infants is periventricular leukomalacia (PVL). PVL is also the most common cause of cerebral palsy in the smallest and most vulnerable preterm infant. The core theme in its pathogenesis is the effect of hypoxia, ischaemia, and inflammation on the vulnerable white matter of the developing brain. Over the last decade, with improved laboratory and imaging techniques, the complex relationships between the known associated factors involved in causation of PVL is becoming increasingly known. A better understanding of its pathogenesis provides the basis for future protective strategies against PVL.     

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.     

UDP-糖、GDNF和美金胺改善新生大鼠缺血性脑白质病变的光电镜病理评估

目的：通过光镜和电镜下脑病理研究,评估单用或联用UDP-糖、胶质细胞源性神经营养因子（GDNF）和美金胺对缺血型脑室周围白质软化（PVL）新生大鼠脑白质病变的改善效果。方法：一侧颈总动脉结扎伴缺氧2 h,建立5日龄新生大鼠PVL模型,随机分为假手术（Sham）组、PVL组、UDP-糖组（PVL后即刻腹腔注射UDP-糖2000 mg/kg）、GDNF组（PVL后即刻脑内注射GDNF 100 μg/kg）、美金胺组（PVL后即刻腹腔注射美金胺20 mg/kg）以及三联药组（PVL后即刻联用UDP-糖、GDNF和美金胺）,每组各30只。每组大鼠分别于造模后7 d及21 d断头取脑,电镜下观察髓鞘形成情况,计算髓鞘数目及厚度;光镜下对脑白质病变进行病理分级及评分。结果：造模后7 d及21 d电镜结果显示,PVL组大鼠罕见髓鞘形成,排列松散,髓鞘壁明显变薄,髓鞘数量及厚度均明显少于Sham组、UDP-糖组、GDNF组、美金胺组及三联药组（P<0.01）。光镜下脑白质病理分级结果显示,PVL组大鼠在造模后7 d和21 d,其脑白质均呈轻度病变（38%~50%）或重度病变（50%~62%）。4个用药组大鼠在造模后7 d和21 d有50%~88%呈正常脑白质,呈重度病变的比例为13%~25%。病理评分显示,PVL组在造模后7 d及21 d的病理评分最高,显著高于其他5组（P<0.05）。结论：单用或联用UDP-糖、GDNF和美金胺可明显改善PVL大鼠脑白质病变。推测良好的改善作用与这些药物能促进脑内源性的神经再生及改善脑微环境密切相关。     

White matter injury after cerebral ischemia in ovine fetuses

The effects of cerebral ischemia on white matter changes in ovine fetuses were examined after exposure to bilateral carotid artery occlusion. Fetal sheep were exposed to 30 min of ischemia followed by 48 (I/R-48, n = 8) or 72 (I/R-72, n = 10) h of reperfusion or control sham treatment (control, n = 4). Serial coronal sections stained with Luxol fast blue/hematoxylin and eosin were scored for white matter, cerebral cortical, and hippocampal lesions. All areas received graded pathologic scores of 0 to 5, reflecting the degree of injury where 0 = 0%, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, 4 = 76% to 95%, and 5 = 96% to 100% of the area damaged. Dual-label immunofluorescence using antibodies against glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were used to characterize white matter lesions. Basic fibroblast growth factor (FGF-2) was measured in the frontal cortex by ELISA. Results of the pathologic scores showed that the white matter of the I/R-72 (2.74 +/- 0.53, mean +/- SEM) was more (p < 0.05) damaged when compared with the control (0.80 +/- 0.33) group. Cortical lesions were greater (p < 0.05) in the I/R-48 (2.12 +/- 0.35) than the control (0.93 +/- 0.09) group. White matter lesions were characterized by reactive GFAP-positive astrocytes and a loss of MBP in oligodendrocytes. The ratio of MBP to GFAP decreased (p < 0.05) as a function of ischemia, indicative of a proportionally greater loss of MBP than GFAP. FGF-2 concentrations were higher (p < 0.05) in the I/R-72 than the control group and there was a direct correlation between the pathologic scores (PS) and FGF-2 concentrations (FGF-2 = e((1.6 PS-0.90)) + 743, n = 17, r = 0.73, p < 0.001). We conclude that carotid artery occlusion results in quantifiable white matter lesions that are associated with a loss of MBP from myelin, and that FGF-2, a purported mediator of recovery from brain injury in adult subjects, increases in concentration in proportion to the severity of brain damage in the fetus.     

Neonatal seizures accompanied by diffuse cerebral white matter lesions on diffusion-weighted imaging are associated with rotavirus infection

Background and aimsSome full-term neonates presenting seizures show diffusion-restricted lesions in the cerebral white matter on brain diffusion-weighted imaging (DWI). The purpose of this study was to describe the clinical characteristics and DWI findings in a group of neonates with seizures, white matter lesions on DWI, and a high incidence of rotavirus infection.MethodsTotal 30 full-term neonates with seizures were admitted between 2008 and 2010. Of these, 13 (group A) had the following characteristics on brain DWI: (1) diffusion-restricted lesions in the diffuse symmetric cerebral white matter, including the corpus callosum, and (2) no cerebral cortical lesions. The remaining 17 patients (group B) did not exhibit the DWI findings. The clinical characteristics were compared between the 2 groups.ResultsThe 1-min and 5-min Apgar scores ranged between 7 and 10 in all group A patients, whereas the scores were more diverse in the group B patients. Patients' age at seizure onset was 4.6 ± 0.6 days (range, 4–6 days) in group A and 8.3 ± 7.4 days (range, 1–27 days) in group B. Twelve of 13 patients (92.3%) in group A tested positive for stool rotavirus antigen, while only 2 of 12 (16.7%) in group B tested positive (p < 0.001). Six of 10 group A patients showed normal neurodevelopment, but 4 had delayed development between 6 and 30 months.ConclusionsRotavirus infection should be considered in neonates with seizures accompanied by diffuse cerebral white matter lesions on DWI, particularly around 5 days of life.     

胰岛素样生长因子-1减少胎羊缺血性脑白质损伤后淀粉样前体蛋白表达(英文)

目的：淀粉样前体蛋白 (β APP)是脑白质损伤早期敏感的指标 ,并参与缺氧缺血性脑损伤机制。本研究观察胎羊缺血性脑白质损伤及胰岛素样生长因子 1(IGF 1)治疗对淀粉样前体蛋白 (β APP)表达的影响。方法：胎羊于胎龄 117 12 4天 (足月为 14 7天 )时通过双侧颈动脉阻塞 30min造成双侧脑缺血损伤 ,损伤后胎羊随机分为损伤组 (n =8)和重组人IGF 1(rhIGF 1)治疗组 (n =9) ;另设正常对照组 (n =5 ) ,为假手术动物。治疗组缺血后 90min经侧脑室注射 3μgrhIGF 1;损伤组经侧脑室注射等量人工脑脊液。缺血损伤后 96h结束实验 ,处死动物 ,取出胎羊 ,固定脑组织。免疫组化法检测脑白质胶质原纤维酸性蛋白 (GFAP)、β APP阳性细胞及白质内髓鞘碱性蛋白 (MBP)密度。应用免疫荧光双标记观察APP表达阳性细胞。结果：与正常对照组 (2 7.8± 4 .8)比较 ,缺血损伤组MBP密度 (4.7± 7.1,P <0 .0 0 1)明显减少。正常对照组未见 β APP阳性细胞 ,损伤后阳性细胞数明显增加 (49.6± 2 3.7,P <0 .0 0 1) ,rhIGF 1治疗可减少 β APP阳性细胞数 (17.9± 16 .5 ,P <0 .0 1)。免疫荧光双标记显示部分细胞为 β APP GFAP双标阳性细胞。 结论：胎羊缺血性脑白质损伤可导致星形胶质细胞表达β APP ,β APP表达增加可能与脑损伤有关     

脑性瘫痪患儿脑白质数量的CT图像及模糊判据分析

目的 利用CT图像,分析脑性瘫痪患儿脑白质数量减少程度,并对脑白质数量减少进行模糊判据分析.方法 选择1 ～3岁临床诊断为脑性瘫痪病例,根据CT检查结果筛选出未见异常、脑白质偏少、脑室旁脑白质软化(PVL)3类病例.将这3类病例,依照年龄每3个月分为一小组,每一小组随机选取6例,共分为24个小组,共144例.利用CT工作站软件测量每例患儿半卵圆层面的脑白质和大脑半球的面积并进行统计分析;根据脑白质面积与大脑半球面积的比值对脑白质减少的性质进行疾病隶属度的模糊判据.结果 1.未见异常组、脑白质偏少组和PVL组患儿脑白质面积数量的中位数依次为2 000 mm2、1 738 mm2和1 387 mm2,未见异常组与脑白质偏少组、PVL组之间的差异均有统计学意义(P ＜0.05,0.01);脑白质偏少组与PVL组间差异无统计学意义(P＞0.05).2.大脑半球面积的中位数分别为5 809 mm2、5 618 mm2和5 370 mm2,3组间的差异均无统计学意义(Pa＞0.05).3.脑白质数量的隶属度图显示脑白质偏少组与PVL组、未见异常组均有交集,但是与PVL组有更多交集;当脑白质与大脑半球的面积比值＜ 0.255时,患儿属于PVL的隶属度≥0.5.结论 影像科诊断医师对脑白质数量的评估较为准确;脑白质偏少可视为轻度PVL.计算半卵圆脑白质与大脑半球的面积比值并由此确认脑白质减少的隶属度对确认病情的严重程度有参考意义.     

足月儿早产儿痉挛型脑性瘫痪CT的对比研究

目的：研究足月儿与早产儿痉挛型脑性瘫痪的CT表现。方法：回顾性分析88例痉挛型脑性瘫痪患儿CT表现,分早产儿和足月儿两组分析,其中46例足月儿,42例早产儿。结果：88例痉挛型脑性瘫痪患儿CT表现的阳性率78.4%(69/88)。主要是脑室周围白质软化(PVL)后遗改变,为47/88例,其中足月儿17例,早产儿30例,两组差异有显著性意义(P<0.05);PVL白质减少可发生于侧脑室体中前部、侧脑室体后部、侧脑室三角区、半卵圆中心,两组间白质减少和侧脑室扩大部位差异无显著性意义;而侧脑室形态不规则扩大在早产儿30例中有7例,足月儿侧脑室扩大未见不规则改变,两组差异有显著性意义(P<0.05)。结论：痉挛型脑性瘫痪CT主要表现为PVL后遗改变,早产儿出现PVL和重度PVL的概率明显大于足月儿。