Gray matter volume decrements in preterm children with periventricular leukomalacia

Periventricular leukomalacia (PVL) is the prototypic lesion in the encephalopathy of prematurity. Although PVL is identified by targeting cerebral white matter (WM), neuropathological and MRI studies document gray matter (GM) loss in cortical and subcortical structures. This study aimed to investigate the distribution of GM changes in children with a history of premature birth and PVL. Voxel-based morphometry was used to examine regional GM abnormalities in 22 children with a history of preterm birth and PVL. Preterms with PVL were compared with 22 terms and 14 preterms without PVL of similar GA and birth weight. GM and WM global volumetric volumes were found to decrease in comparison with both control groups. Regional GM volume abnormalities were also found: compared with their term peers, preterm children with PVL showed several regions of GM reduction. Moreover, PVL differed from preterms without PVL in the medial temporal lobe bilaterally, thalamus bilaterally, and caudate nuclei bilaterally. In addition, in our preterm sample with PVL, birth weight showed a statistical significant correlation with decreased GM regions. In conclusion, the voxel-based morphometry methodology revealed that PVL per se does involve GM reductions.     

早产儿暂时性低甲状腺素血症与脑损伤及神经行为学相关性研究

目的 通过对早产儿甲状腺素水平测定及脑、神经行为发育测评,分析甲状腺素水平与脑损伤、神经行为学的相关性.方法 选取2009年11月至2010年4月,上海交通大学附属上海市儿童医院新生儿科收治的早产儿52例,生后6 h内留取血清样本,放射免疫法测定T3、T4、TSH值.所有患儿出生后3 d行头颅B超检查,每周复查1次,出院前行头颅MRI检查.根据头颅MRI结果将患儿分为3组:无脑损伤组(33例)、脑室内出血组(10例)、脑白质损伤组(9例).所有患儿于纠正胎龄40±2周时行新生儿20项行为神经测定.结果 3组患儿TSH均正常,排除先天性甲状腺功能减低症;共8例早产儿甲状腺功能正常,占15.4%(8/52);另44例早产儿甲状腺功能均低下,占84.6%(44/52).无脑损伤组T3、T4水平高于脑室内出血组及脑白质损伤组,并以脑白质损伤组T3、T4水平最为低下,3组间比较差异有统计学意义(P＜0.05).无脑损伤组患儿行为能力、被动肌张力、主动肌张力及总分4项得分显著高于有脑损伤的两组患儿,且脑室内出血组患儿得分又高于脑白质损伤组患儿,3组间比较差异有统计学意义(P＜0.05).结论 早产儿脑损伤越严重,甲状腺素水平越低.有脑损伤的早产儿神经行为学评分较无脑损伤的早产儿低.     

三碘甲腺原氨酸对新生小鼠兴奋毒性脑损伤病理改变及Caspase-3和髓鞘碱性蛋白表达的影响

目的 探讨腹腔注射不同剂量三碘甲腺原氨酸(T3)对新生小鼠兴奋毒性脑损伤脑组织病理改变和Caspase-3、髓鞘碱性蛋白(MBP)表达的影响.方法 72只新生5日龄(P5)ICR小鼠随机分为PBS对照组(PBS组)、兴奋毒性脑损伤模型组(IA组)、T3低剂量治疗组(LT组)、T3中剂量治疗组(MT组)和T3高剂量治疗组(HT组).模型组及T3各剂量治疗组脑内注射鹅膏蕈氨酸建立兴奋毒性脑损伤模型,模型建立后腹腔注射3种不同剂量(2 μg·kg-1、5 μg·kg-1、10 μg·kg-1)T3共5 d干预治疗.于脑内注射后120 h(P10)、30 d(P35)各取6只小鼠处死,HE染色观察其脑组织病理改变.免疫组织化学法检测小鼠脑组织损伤区Caspase-3及MBP的表达.结果 P10时,MT组脑白质及皮质损伤较IA组均明显减轻(Pa＜0.01),HT组脑皮质损伤较IA组减轻(P＜0.05);IA组Caspase-3表达较PBS组明显增强(P＜0.001),MT组和HT组Caspase-3表达与IA组比较明显减低(P＜0.01);P10和P35时,IA组MBP表达较PBS组均明显减弱(P＜0.001),MT组和HT组MBP表达较IA组均明显增强(P＜0.05).LT组脑组织病理损伤程度及Caspase-3、MBP表达与IA组比较差异均无统计学意义(Pa＞0.05).结论 腹腔注射中剂量及高剂量T3可减轻小鼠兴奋毒性脑损伤病理损伤程度,减少细胞凋亡,促进髓鞘的形成;低剂量T3对新生小鼠兴奋毒性脑损伤程度、细胞凋亡及髓鞘形成均无影响.     

Glycine antagonist and NO synthase inhibitor protect the developing mouse brain against neonatal excitotoxic lesions

The prevention of cerebral palsy and neuroprotection of the immature brain continue to be health care priorities. The pathophysiology of perinatal brain lesions associated with cerebral palsy seems to be multifactorial and includes pre- and perinatal factors such as preconceptional events, hormone and growth factors deficiencies, maternal infections with production of cytokines, and hypoxic/ischemic perfusion failures. Excitotoxic cascade could represent a common pathway that leads to neural cell death and subsequent brain damage. Brain injuries induced by ibotenate, a glutamatergic analog, which are essentially mediated through the N-methyl-D-aspartate receptor, mimic some aspects of the white matter cysts and transcortical necrosis observed in human perinatal brain damage. The purpose of the present study was to assess the protective role of several pharmacological agents, administered in conjunction with ibotenate, against induced excitotoxic lesions. We injected ibotenate in the developing mouse brain 5 d postnatally, after the full settlement of neuronal layers. Co-treatment with kynurenic acid, an antagonist of the facilitating glycine site of the N-methyl-D-aspartate receptor, or with N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, induced a dose-dependent neuroprotective effect. Conversely, zinc gluconate, a blocking agent of the channel linked to the N-methyl-D-aspartate receptor, and a free radical scavenger (U74389F), were unable to protect the developing brain against excitotoxic attack. These data help to clarify some molecular mechanisms involved in excitotoxic lesions of the developing mouse brain and permit us to envision new strategies in the prevention of cerebral palsy.     

Arterial spin-labeled perfusion combined with segmentation techniques to evaluate cerebral blood flow in white and gray matter of children with sickle cell anemia

Background

Changes in cerebral perfusion are an important feature of the pathophysiology of sickle cell anemia (SCA); cerebrovascular ischemia occurs frequently and leads to neurocognitive deficits, silent infarcts, and overt stroke. Non‐invasive MRI methods to measure cerebral blood flow (CBF) by arterial spin labeling (ASL) afford new opportunities to characterize disease‐ and therapy‐induced changes in cerebral hemodynamics in patients with SCA. Recent studies have documented elevated gray matter (GM) CBF in untreated children with SCA, but no measurements of white matter (WM) CBF have been reported.

Procedures

Pulsed ASL with automated brain image segmentation‐classification techniques were used to determine the CBF in GM, WM, and abnormal white matter (ABWM) of 21 children with SCA, 18 of whom were receiving hydroxyurea therapy.

Results

GM and WM CBF were highly associated (R² = 0.76, P < 0.0001) and the GM to WM CBF ratio was 1.6 (95% confidence interval: 1.43–1.83). Global GM CBF in our treated cohort was 87 ± 24 mL/min/100 g, a value lower than previously reported in untreated patients with SCA. CBF was elevated in normal appearing WM (43 ± 14 mL/min/100 g) but decreased in ABWM (6 ± 12 mL/min/100 g), compared to published normal pediatric controls. Hemispheric asymmetry in CBF was noted in most patients.

Conclusions

These perfusion measurements suggest that hydroxyurea may normalize GM CBF in children with SCA, but altered perfusion in WM may persist. This novel combined approach for CBF quantification will facilitate prospective studies of cerebral vasculopathy in SCA, particularly regarding the effects of treatments such as hydroxyurea. Pediatr Blood Cancer 2009;52:85–91. © 2008 Wiley‐Liss, Inc.     

Effects of antenatal steroids on ischemic brain injury in near-term ovine fetuses

BACKGROUND: Hypoxia/ischemia in utero can result in brain damage to the fetus and newborn. Antenatal steroids are a routine part of the management of women who develop premature labor. Pretreatment of young postnatal rats with dexamethasone before hypoxic/ischemic insults has been reported to attenuate brain injury. However, the effects of antenatal steroids on ischemic brain injury in fetuses have not been investigated. OBJECTIVE: We examined the effects of maternally administered antenatal corticosteroids on ischemic brain injury in near-term ovine fetuses. METHODS: Chronically instrumented fetuses at 122 days of gestation were studied 12 h after the last of four 4 mg dexamethasone, or placebo injections were given over 48 h to the ewes. Groups were dexamethasone/ischemic, placebo/ischemic and sham-treated control. Fetuses were exposed to 30 min of carotid occlusion (ischemia) or no occlusion (control) and 72 h of reperfusion. Whole brain coronal sections stained with Luxol fast blue-hematoxylin-eosin were scored for white matter and cerebral cortical lesions. Both areas received pathological scores of 0 to 5 reflecting the degree of injury (0=0%, 1=1-10%, 2=11-50%, 3=51-90%, 4=91-99% and 5=100%). Bilateral carotid blood flow also was measured before, during and after brain ischemia in the dexamethasone/ischemic and placebo/ischemic groups. RESULTS: White matter (WM) and cerebral cortical scores did not differ between the dexamethasone/ischemic and placebo/ischemic (WM: 3.0+/-1.9 and 2.9+/-1.7; cortex: 3.1+/-1.7 and 2.6+/-1.8, mean+/-S.D.) groups. White matter and cerebral cortical scores were higher in the dexamethasone/ischemic (WM: 3.0+/-1.9, P<0.02; cortex: 3.1+/-1.7, P<0.005) and placebo/ischemic (WM: 2.9+/-1.7, P<0.006; cortex: 2.6+/-1.8, P<0.007) than control (WM: 0.2+/-0.4; cortex: 0.2+/-0.4) group. Carotid blood flow was relatively higher (P<0.05) after 24, 48 and 72 h of reperfusion in the dexamethasone/ischemic than placebo/ischemic group. CONCLUSIONS: We conclude that maternal pretreatment with antenatal dexamethasone did not attenuate ischemic brain injury in the fetus, and that carotid blood flow was higher during reperfusion in fetuses of dexamethasone than placebo-treated ewes, most likely secondary to decreases in arterial oxygen tension.     

Effects of exogenous glucose on brain ischemia in ovine fetuses

We examined the effects of prolonged moderate hyperglycemia with and without an additional rapid glucose injection on ischemic brain injury in the fetus. Twenty-five ewes (117-124 d of gestation) were assigned to one of four groups: 1) glucose-infused fetuses exposed to 30 min of carotid artery occlusion followed by 48 h of reperfusion (I/R-Glu, n = 8); 2) glucose-infused plus rapid glucose injection given 100 min before 30 min of occlusion followed by 48 h of reperfusion (I/R-GluR, n = 4); 3) placebo-infused exposed to 30 min of occlusion and 48 h of reperfusion (I/R-PL, n = 8); and 4) glucose-infused sham occlusion and 48 h of sham reperfusion (control, n = 5). After baseline measurements, fetuses were infused with glucose (9-16 mg/kg/min) for 48 h before and after carotid occlusion or sham treatment. The I/R-PL group received 0.9% NaCl. Brain pathologic outcome was determined. Serial sections stained with Luxol fast blue-hematoxylin and eosin were scored for white matter, cerebral cortical, and hippocampal lesions. These areas received graded pathologic scores of 0 to 5, reflecting the amount of injury, where 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-95%, and 5 = 96-100% of the area damaged. Comparisons of the pathologic scores for cerebral cortex (CC), white matter (WM), and hippocampus (H) demonstrated that the I/R-GluR (CC: 4.56 +/- 0.11, WM: 4.50 +/- 0.11, H: 3.44 +/- 0.48, mean +/- SEM) had more (p < 0.05) damage than the I/R-Glu (CC: 2.46 +/- 0.47, WM: 1.97 +/- 0.37, H: 1.81 +/- 0.36) and control (CC: 1.12 +/- 0.13, WM: 0.82 +/- 0.34, H: 0.80 +/- 0.34) groups. The pathologic scores in the I/R-Glu were (p < 0.05) greater than the control, but not the I/R-PL (CC: 2.12 +/- 0.35, WM: 2.20 +/- 0.44, H: 1.59 +/- 0.41) group. We conclude that exposure to prolonged moderate hyperglycemia before ischemia and during reperfusion does not affect the extent of brain injury, but exposure to an additional acute increase in plasma glucose concentration before ischemia is extremely detrimental to the fetal brain.     

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.     

Thyroid dysfunction in multi-transfused iron loaded thalassemia patients.

Seventy-two transfusion-dependent iron loaded thalassemia patients were investigated for thyroid dysfunction by estimating circulating thyroid hormones (T4 and T3) and basal thyroid stimulating hormone (TSH). They were also evaluated for their liver function (biochemically) and iron overload by estimating serum ferritin. Thyroid failure (hypothyroidism) was documented in 14 patients (19.4%). In all, 3 groups were seen, i.e. Group 1: Normal T4, T3, TSH (58 patients: 80.6%); Group 2: Compensated hypothyroidism characterized by normal T4, T3 and raised TSH (9 patients: 12.5%); Group 3: Decompensated hypothyroidism characterized by decreased T4 and increased TSH (5 patients: 6.9%). Interestingly, impaired thyroid function could not be correlated with age, amount of blood transfused, liver dysfunction or degree of iron overload. It is postulated that an inter-play between chronic hypoxia, liver dysfunction and iron overload may be responsible for the thyroid damage.     

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.     

Follow-up of newborns with elevated screening T4 concentrations

OBJECTIVE: To determine the type and incidence of hyperthyroxinemic disorders detected by follow-up of infants with elevated screening total T4 (TT4) values. STUDY DESIGN: Infants born in Oregon with a screening TT4 measurement >3 SD above the mean were offered enrollment. Serum TT4, free T4, total T3, free T3, and thyroid-stimulating hormone concentrations were measured in study infants and their mothers. RESULTS: Over a 20-month period, 101 infants (51 boys) and their mothers enrolled in the study (of 241 eligible infants), from a total screening population of 80,884; 17 infants were identified with persistent hyperthyroxinemia (TT4 >16 microg/dL). Ten had thyroxine-binding globulin excess (1:8088), 5 had evidence for increased T4 binding but not thyroxine-binding globulin excess (1:16,177), and 2 had findings compatible with thyroid hormone resistance (1:40,442); the other 84 infants had transient hyperthyroxinemia. Sequence analysis revealed a point mutation in the thyroid hormone receptor-beta gene in one infant with thyroid hormone resistance; no mutation was identified in the other infant. CONCLUSIONS: Although neonatal Graves' disease occurs in approximately 1 in 25,000 newborn infants, we did not detect any case among 80,884 infants, most likely because their mothers were receiving antithyroid drugs. Although the other hyperthyroxinemic disorders in the aggregate occur frequently (1:4758) and may benefit from detection, in general they do not require treatment.     

Postnatal changes in cerebral oxygen extraction in the preterm infant are associated with intraventricular hemorrhage and hemorrhagic parenchymal infarction but not periventricular leukomalacia

Fluctuations in cerebral hemodynamics have been implicated in the pathogenesis of acquired brain damage in babies born prematurely. This study examined the changes in cerebral fractional oxygen extraction (FOE) over the first 3 d after birth in 25 very-low-birth-weight preterm infants. Twelve infants had no major cerebral injury and 13 had acquired brain injury; cystic periventricular leukomalacia (PVL) was present in 4 and intraventricular hemorrhage (IVH) in 9, of whom 2 also had hemorrhagic parenchymal infarction (HPI). Normal values (median, 5(th)-95(th) centiles) for cerebral FOE in very-low-birth-weight infants with no cerebral injury were 0.38 (0.23-0.53) on d 1, 0.31 (0.18-0.45) on d 2, and 0.28 (0.17-0.38) on d 3. Infants who developed cystic PVL had no significant change in cerebral FOE during the first 3 d after birth. By contrast, cerebral FOE fluctuated in infants with IVH over the 3 d of measurement, decreasing from d 1 to d 2 (p = 0.03) and increasing from d 2 to d 3 (p = 0.02). The highest cerebral FOE values were seen in the two infants with HPI. The different patterns of change in cerebral FOE with HPI and cystic PVL provide additional evidence that the pathogenesis of these two conditions is different. Because high cerebral FOE is likely to be a consequence of low cerebral oxygen delivery, probably because of low cerebral blood flow, our results indicate that fluctuations in cerebral blood flow may occur when there is IVH or HPI.     

Hormonal factors in the morbidities associated with extreme prematurity and the potential benefits of hormonal supplement.

Cortisol and thyroid hormones are known to modulate the maturation of various fetal organ systems, enzymes, and biochemical pathways. The cortisol furnished by the structural and biochemical immature fetal adrenal gland renders the extremely premature infants relatively cortisol deficient in comparison with the term newborns. The premature infants also have elevated fetal androgens, the production of which persists until approximately 42 weeks of postconceptional age. The androgens produced by the fetal adrenal cortex and the müllerian inhibiting substance produced by the fetal testis have antiglucocorticoid and inhibitory effects on human fetal lung growth and maturation in vitro. Hypothalamic-pituitary-thyroid axis and thyroid function are also immature in extreme prematurity. In addition, there is reduced tissue thyroid hormone responsiveness. Superimposed on this is the reduced thyroid function seen in non-thyroidal illness in which elevated cytokine levels have been implicated. Repeated courses of antenatal steroids and high-dose postnatal dexamethasone appear to be deleterious to lung and brain development. This may be through inhibition of cell replication and catabolism as well as decreased thyroid-stimulating hormone secretion and reduced peripheral conversion of T(4) to T(3). Furthermore, dexamethasone has been found to enhance neurosteroid production in the immature brain, potentially altering brain development. Considered together, the relative cortisol deficiency/androgen excess and reduced thyroid function as well as prolonged high-dose postnatal dexamethasone therapy in these infants may be important factors in their high degree of morbidity. We propose to restrict antenatal steroids to a single course and hypothesize that the overall outcome of low-gestation infants would be improved with (1) hydrocortisone (i.v./p.o.) supplement at a fixed dose of 0.5 mg/kg birth weight every 12 h in infants <30 weeks of gestation from birth till 32 weeks of postconceptional age and (2) T(3) (i.v./p.o.) supplement at a fixed dose of 0.4 microg/kg birth weight every 12 h in those <27 weeks of gestation from birth till 32 weeks of postconceptional age.     

Relation of thyroid hormone levels with fluid-resistant shock among preterm septicemic neonates

Objective

To compare thyroid hormone levels between septicemic preterm neonates with and without shock.

Methods

Preterm septicemic infants with shock constituted Group A (n=36) and those without shock constituted Group B, with groups matched (1:1) for gestation and postnatal age. Those with maternal thyroid disorders, thyrotropic medication and life expectancy <12 hours were excluded. We compared serum tri-iodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) between the groups by univariate and multivariate (adjusting for SNAPPE-II) analysis.

Results

Median (IQR) TSH was significantly lower in Group A [1.39 (0.83,3.48)] vs Group B [5.1 (2.32,7.19)] mmol/dL (P<0.001). Serum T3 and T4 were also lower in Group A (P<0.001). On multivariate analysis, none of these measures were independently associated with septic shock.

Conclusions

Thyroid hormone levels do not independently predict presence of shock among septic preterms.

     

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。     

药物干预幼大鼠缺氧缺血性脑损伤与p53蛋白表达的研究

目的通过检测缺氧缺血性脑损伤(HIBD)幼大鼠脑组织中p53蛋白的表达和一氧化氮(NO)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)含量,探讨HIBD的发病机制;了解神经节苷酯(GM1)和胞二磷胆碱干预对HIBD的影响。方法80只Wistar幼大鼠随机分四组;对照组、缺氧缺血组、GM1组、胞二磷胆碱组。17日龄制作HIBD模型,24 h后处死检测脑组织中p53蛋白的表达和NO、NOS、SOD含量及组织形态学的变化。结果缺氧缺血组NO、NOS含量高于其他三组(P<0.05);缺氧缺血组与胞二磷胆碱组SOD含量低于对照组和GM1组(P<0.05);缺氧缺血组p53蛋白表达高于其他三组(P<0.01),GM1和胞二磷胆碱组p53蛋白表达高于对照组(P<0.01);组织形态学改变显示,缺氧缺血组变性、坏死严重,GM1组与胞二磷胆碱组次之,对照组正常。结论NO和自由基引起的组织损伤可能诱导p53蛋白表达导致HIBD。GM1和胞二磷胆碱能改善脑组织NO、NOS、SOD含量和p53的表达,提示GM1和胞二磷胆碱对HIBD有一定的保护作用。     

How should we be treating children with congenital hypothyroidism?

Early detection by newborn screening and appropriate L-thyroxine treatment leads to normal or near-normal neurocognitive outcome in infants with congenital hypothyroidism. Many newborns with congenital hypothyroidism have some residual thyroid hormone production, and even in those with athyreosis, transplacental passage of maternal thyroid hormone offers some protection for a time. Given the serum T4 half-life of 6 days, the neonatal T4 level will fall and disappear over the first 2-3 weeks of life. Thus, there is a crucial 'window of opportunity' to correct the hypothyroidism and minimize the time the brain is exposed to hypothyroxinemia. While there are few truly prospective, randomized clinical trials investigating treatment parameters, studies measuring IQ outcome support a starting L-thyroxine dose of 10-15 microg/kg/day. Further, studies show that the most severely hypothyroid infants are at risk for a 5-20 point decrease in IQ. Such infants may benefit from a starting dose of 12-17 microg/kg/d, which has been shown to normalize T4 in 3 days and TSH in 2 weeks. Target serum T4 or free T4 levels appear to be higher in the first two weeks of treatment. Infants require more frequent laboratory monitoring, every 1-2 months in the first 6 months and every 3-4 months until age 3 years, as the developing brain has a critical dependence on thyroid hormone in the first 2-3 years of life.     

High-field diffusion tensor imaging characterization of cerebral white matter injury in lipopolysaccharide-exposed fetal sheep

Background:In gyrencephalic species such as sheep, precise anatomical and microstructural characterization of the consequences of fetal inflammation remains scarce. The goal of this study was to characterize changes in white matter (WM) structure using advanced magnetic resonance imaging (MRI) following lipopolysaccharide (LPS) exposure in the preterm-equivalent fetal sheep.Methods:Preterm (0.7 gestation) fetal sheep received vehicle (Sham group) or LPS (LPS group), and fetal brains were collected 10 d later for subsequent ex vivo MRI. T(1)-weighted (T(1)W), T(2)-weighted (T(2)W), and diffusion tensor imaging (DTI) data were collected.Results:Fetuses exposed to LPS exhibited reductions in WM volume and corpus callosum thickness at 10 d recovery. Characteristic patterns of diffuse and focal WM lesions (necrosis or cysts) could be identified by various T(1), T(2), and DTI signal changes.Conclusion:Fetal LPS exposure induces a pattern of injury characterized by diffuse and focal WM injury that closely reproduces that observed clinically in preterm infants. This work provides anatomical and microstructural MRI assessment, as well as histopathological correlates, of the consequences of LPS exposure in an animal model with a WM structure similar to that of the human brain. This work will help to further our understanding of MRI changes in preterm infants.     

早产儿脑室周围白质软化的影像学改变及其对预后的影响

脑室周围白质软化( periventricular leukomalacia, PVL)是早产儿具有特征性的脑损伤形式之一,易造成小儿神经系统后遗症,严重影响小儿以后的运动发育和生活质量。早产儿PVL无特异性症状,诊断依赖于影像学检查。经颅超声能对PVL做出初步诊断及预后评价。结合MRI可评价PVL患儿的损伤程度,预测可能发生的不良后果,为早期治疗提供依据。该文对早产儿PVL的影像学改变及其对预后的影响进行综述。     

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.