Complicaciones neurológicas de la prematuridad / Neurological consequences of prematurity

Resumen Los nacimientos prematuros representan un in dicador importante de salud de un país. Estos niños tienen un mayor riesgo de mortalidad y morbilidad. Las principales lesiones encefálicas en los prematuros incluyen lesiones de la sustancia blanca, hemorragias intracraneanas y lesiones cerebelosas, que pueden ser detectadas mediante ecografía encefálica y resonancia magnética, siendo esta última la técnica más sensible. Estas lesiones pueden tener repercusión a largo plazo en el neurodesarrollo de los prematuros, con un mayor riesgo de parálisis cerebral, trastornos cognitivos, con ductuales, sensoriales y del aprendizaje, entre otros. Es fundamental aplicar estrategias de prevención y aten ción temprana para reducir las consecuencias negativas de las lesiones encefálicas asociadas a la prematuridad.

Abstract Premature births are an important health indicator for a country. These children have a higher risk of mor tality and morbidity. The main brain injuries in preterm infants include white matter injuries, intracranial hem orrhages, and cerebellar injuries. These injuries can be detected through brain ultrasound and magnetic reso nance imaging (MRI), with MRI being the most sensitive technique. Perinatal brain injuries may have long-term consequences on the neurodevelopment of preterm infants, with an increased risk of cerebral palsy, cogni tive, behavioral, sensory, and learning disorders, among others. It is key to implement prevention strategies and early intervention to reduce the negative consequences of brain injuries associated with prematurity.

Corioamnionitis histológica y neurodesarrollo en niños prematuros menores de 34 semanas, Lima-Perú

Para determinar los efectos de la corioamnionitis histológica en el neurodesarrollo de los prematuros menores de 34 semanas evaluados a los 2 años de edad corregida se realizó un estudio secundario de casos y controles. Fueron analizados los datos clínicos, hallazgos histológicos de la placenta e índices del desarrollo medidos por la Escala Bayley III de 38 niños expuestos y 53 niños no expuestos. Las infecciones genitourinarias de la madre y la sepsis precoz fueron más frecuentes en el grupo expuesto (p<0,005). Las dimensiones del desarrollo cognitivo, motor y lenguaje fueron normales en ambos grupos. Los expuestos al subtipo subcorionitis obtuvieron menor desempeño en las tres dimensiones. La corioamnionitis histológica no mostró influencia sobre el neurodesarrollo en prematuros menores de 34 semanas a los 2 años de edad. Se recomienda estudios longitudinales y multicéntricos para definir los efectos a largo plazo.

SUMMARY The objective of this study was to determine the effects of histologically diagnosed chorioamnionitis on neurodevelopment of premature babies born with less than 34-week gestational age who were assessed at two-year corrected age. A secondary case-control study was carried out. Clinical data, placental histological findings, and development indexes assessed using the Bayley III scale were analyzed in 38 exposed children and 53 non-exposed children. Genitourinary infections in mothers and early sepsis were more frequent in the exposed group (p<0.005). Cognitive development, motor development and language were normal in both groups. Those children exposed to the chorionitis subtype had lower scores in the aforementioned variables. Histologically diagnosed chorioamnionitis did not show any influence on neurodevelopment in premature babies born with less than 34-week gestational age when they were assessed at two years. Longitudinal and multicenter studies are advised in order to define the long-term effects.

Glaucoma-simulating cupping in a patient with periventricular leukomalacia: a clinical case report / Escavação simulando glaucoma em paciente com leucomalácia periventricular: relato de caso clínico

ABSTRACT Non-glaucomatous papillary cupping constitutes an important differential diagnosis in daily medical practice. There are patients diagnosed and treated as glaucoma, who do not present the disease and are part of the large group of non-glaucomatous optic neuropathies. This case emphasizes directing the diagnostic gaze to these "apparently glaucomatous" optic nerves through a case of periventricular leukomalacia. Patients with a history of prematurity, alterations in the cerebral white matter and presence of optic nerve excavations with normal intraocular pressures.

RESUMO A escavação papilar não glaucomatosa constitui um importante diagnóstico diferencial na prática médica diária. Há pacientes que recebem o diagnóstico de e tratamento para glaucoma, que não apresentam a doença e fazem parte do grande grupo de neuropatias ópticas não glaucomatosas. Este caso enfatiza o direcionamento do olhar diagnóstico para nervos ópticos "aparentemente glaucomatosos" através de um episódio de leucomalácia periventricular. Pacientes com histórico de prematuridade, alterações na substância branca do cérebro e presença de escavações do nervo óptico com pressões intraoculares normais.

Tamaño del léxico en niños(as) muy prematuros y prematuros extremos de 24 meses: un estudio transversal / Vocabulary size in very preterm and extremely preterm infants: a cross-sectional study

Las investigaciones muestran que un número importante de niños nacidos prematuros (antes de las 37 semanas de gestación) presentan dificultades en su desarrollo, entre ellas el desarrollo lingüístico. Las investigaciones previas indican que algunas complicaciones biomédicas, como la hemorragia intraventricular (los grados III y IV), la leucomalacia periventricular y la displasia broncopulmonar, incrementan la probabilidad de presentar alteraciones en el desarrollo de la cognición y/o del lenguaje, por lo que se hace necesario realizar investigaciones que proporcionen más información y con ello poder anticiparse a posibles consecuencias en los aprendizajes futuros de estos niños nacidos bajo la condición de prematuridad. Es así, que los objetivos de este estudio fueron medir el tamaño del léxico temprano en niños muy prematuros y prematuros extremos (con y sin complicaciones biomédicas) a los 24 meses de edad corregida, así como también determinar la asociación entre número de complicaciones biomédicas presentes y el tamaño del léxico. Para ello, se trabajó con 108 niños divididos en tres grupos: 39 niños prematuros de alto riesgo (con complicaciones biomédicas), 36 niños prematuros de bajo riesgo (sin complicaciones biomédicas asociadas a alteraciones del lenguaje y /o cognición) y 33 niños nacidos de término. Todos fueron evaluados con el Inventario II de Desarrollo de Habilidades Comunicativas MacArthur-Bates. Los resultados muestran que los niños nacidos de término tienen significativamente mayor tamaño del léxico que los prematuros, no existiendo diferencias en los resultados entre prematuros de bajo riesgo y los prematuros de alto riesgo. Por otra parte, el tamaño del léxico no presenta correlación con las complicaciones biomédicas.

Research shows that a significant number of children born preterm (before 37 weeks of gestation) have developmental difficulties, among them disturbances in language development. Studies indicate that some biomedical complications such as intraventricular hemorrhage (grades III and IV), periventricular leukomalacia, and bronchopulmonary dysplasia increase the probability of cognitive and/or language development disorders. Therefore, there is a need to conduct more studies that provide information that allows anticipating possible consequences in the learning process of children born prematurely. The aims of this study were to measure the early vocabulary size in very preterm and extremely preterm children (with and without biomedical complications) at 24 months of corrected age and to determine the association between the number of biomedical complications and vocabulary size. To that effect, we worked with 108 children divided into three groups: 39 high-risk preterm children (with biomedical complications), 36 low-risk preterm children (without biomedical complications associated with language and/or cognitive disturbances), and 33 full-term children. All children were evaluated using the MacArthur-Bates Communicative Development Inventory II. The results show that the vocabulary size of full-term children is significantly larger than that of preterm children and that no differences exist between the group of high-risk versus low-risk preterm children. On the other hand, vocabulary size does not correlate withbiomedical complications.

Ocular signs, visual and general developmental outcome in Indian children with radiologically proven periventricular leukomalacia

Purpose: Owing to the paucity of literature on Indian children with periventricular leukomalacia (PVL), this retrospective study aimed to describe the visual and associated developmental abnormalities in a series of affected children attending a tertiary level eye care facility. Methods: Children with radiologically confirmed PVL who attended the Pediatric Department of a tertiary eye hospital were included and underwent a detailed ocular and general developmental assessment. Results: Of the 75 children, the mean age was 2.3 years, the mean follow?up was 3.1 years, 68% were males and 43% were born preterm. Grade I PVL was identified in 13 children (17%), Grade 2 PVL in 39 (52%), and Grade 3 PVL in 23 (31%). Premies with ?2 kg (72.5%) and term babies with >2 kg (75%) had a greater association of PVL occurrence with a preponderance to severe PVL; 46% of the children were visually impaired which was significantly higher in the children with Grade 3 PVL (74%) than those with Grade 2 PVL (15%). Strabismus was common (80%) with a change in deviation over time. Seventy?one percent of the children had a refractive error, frequently myopic astigmatism. All the children except two had a delay in one or more general developmental milestones. Conclusion: PVL occurrence is observed both in the babies born at term and premies, resulting in significant ocular and systemic morbidities. We recommend a system in place for early identification and referral to initiate an early intervention program which goes a long way toward improving the quality of life in these children

The correlation between γδ-T lymphocyte subset in early postnatal peripheral blood and brain injury of preterm infants / 中华实用儿科临床杂志

Objective:To investigate the correlation between preterm infants with brain injury and the proportion of lymphocyte subsets, especially γδ-T cells in the postnatal peripheral blood, and to determine the predictive potential of γδ-T cells in the early peripheral blood in brain injury.Methods:It was a prospective study involving 106 preterm infants with gestational age less than 34 weeks who were delivered in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University from January 1, to June 1, 2021.Relative levels of γδ-T , CD4 + T, CD8 + T, CD3 + T and total lymphocyte subsets in peripheral blood collected within the first 24 hours after birth were measured by flow cytometry.Recruited infants were divided into brain injury group (36 cases) and non-brain injury group (70 cases) according to serial cranial ultrasound and magnetic resonance imaging(MRI) at the corrected gestational age of 36-37 weeks.Differences in general conditions and the proportion of lymphocyte subsets between groups were compared by the t-test or Chi- square test.Patients in brain injury group were further divided into intracranial hemorrhage(ICH) group(8 cases), periventricular leukomalacia (PVL) group (6 cases)and diffuse white matter damage (WMD) group(22 cases). The proportion of lymphocyte subsets among the different groups was compared by One- Way ANOVA, followed by the LSD- t test. Results:The proportion of γδ-T cells in postnatal peripheral blood of preterm infants at 24 hours after birth in brain injury group was significantly lower than that of non-brain injury group [(0.09±0.12)% vs.0.15±0.13)%, t=-2.445, P=0.016]. No significant differences in the proportion of the CD4 + and CD8 + T cell subsets were found between them.Both preterm infants in PVL group and WMD group had a significantly lower proportion of γδ-T cells at 24 hours after birth compared to that of the non-brain injury group [(0.03±0.05)%, (0.07±0.09)% and (0.15±0.13)%], respectively, ( t=-2.190, -2.659, all P<0.05). Conclusions:γδ-T cells in early postnatal peripheral blood may be involved in the development of brain injury in preterm infants and they had early predictive value for preterm infants at high risk of brain injury, especially the leukomalacia and diffuse white matter injury.

Postnatally confirmed COL4A1 mutation in a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia / 中华围产医学杂志

We report a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia during pregnancy who was postnatally detected with a de novo mutation in the COL4A1 gene by genetic testing of umbilical cord blood. Multiple fresh hemorrhagic foci were detected in the fetal brain parenchyma and cerebellar hemisphere by ultrasound at 25 gestational weeks. Regular re-examination of the nervous system's ultrasound and magnetic resonance imaging (MRI) indicated recurrent multiple intraparenchymal hemorrhages followed by cystic leukomalacia. However, karyotyping and chromosomal microarray analysis of amniotic fluid showed no abnormality. The newborn was born by cesarean section at 37 +3 gestational weeks with an Apgar score of 10 at 1 and 5 min. Repeated apnea occurred after birth. MRI detected new intraparenchymal hemorrhage and cystic leukomalacia on the six-day of life. The infant's limb muscle tone remained low on the 90-day follow-up. The patient was lost to follow up. Whole-exome sequencing of the cord blood identified a de novo heterozygous mutation- c.4738G>A in the COL4A1 gene (NM_001845.4; p.G1580S) neither parent carried. It suggests that the genetic test of the COL4A1 mutation should be considered for fetuses with intracranial hemorrhage in the prenatal diagnosis, especially those with recurrent fetal intraparenchymal hemorrhage followed by cystic leukomalacia. Genetic tests could help analyze the fetal prognosis, and guide the delivery mode.

Ecografía transfontanelar en la enfermedad hipóxico isquémica del recién nacido. Presentación de un caso / Transfontanellar ultrasound in hypoxic diseasenewborn ischemic. Presentation of a case

RESUMEN La enfermedad hipóxico-isquémica constituye una de las principales causas de morbi-mortalidad neurológica en el recién nacido. Las diferentes adaptacio-nes vasculares a la hipoxia tanto en el neonato pretérmino como en niño a término hacen que su presentación en neuroimagen, sobre todo en el ultrasonido (US) sea caracterizable según el territorio afectado y el momento de la enfermedad. El ultrasonido se ha convertido en una poderosa herramienta para la evaluación del recién nacido con sospecha de EHI, y el patrón de las lesiones tiene importantes implicaciones en el tratamiento y en el pronóstico neurológico a largo plazo. A continuación, presentamos el caso de un recién nacido masculino, prematuro extremo, que requirió reanimación cardiopulmonar avanzada en el nacimiento y que además presento dos episodios de parada cardiorrespiratoria en el segundo y tercer día de vida, en el cual se llegó al diagnóstico con patrones ecográficos característicos de lesión isquémica y además se detalla la evolución de los hallazgos en el tiempo.Palabras claves: Enfermedad hipóxico-isquémica, ultrasonido transfontanelar, matriz germinal, leucomalacia periventricular.

ABSTRACT Hypoxic-ischemic disease is one of the main causes of neurological morbidity and mortality in the newborn. The different vascular adaptations to hypoxia in both the preterm and term infants make their presentation on neuroimaging, especially on ultrasound (US), characterizable according to the affected terri-tory and the time of the disease. Ultrasound has become a powerful tool for evaluating the newborn with suspected IBD, and the pattern of the lesions has important implications for treatment and long-term neurological prognosis. Next, we present the case of a male newborn, extremely premature, who required advanced cardiopulmonary resuscitation at birth and who also presented two episodes of cardiorespiratory arrest on the second and third day of life, in which the diagnosis was reached with patterns sonographic characteristics of ischemic injury and also the evolution of the findings over time.Keywords: Hypoxic-ischemic disease, transfontanelar ultrasound, germ matrix, periventricular leukomalacia

Hemorragia intraventricular y leucomalacia periventricular en neonatos de bajo peso al nacer en tres hospitales de Lima, Perú / Intraventricular hemorrhage and periventricular leukomalacia in low birth-weight neonates in three hospitals in Lima, Peru

RESUMEN Con el objetivo de describir la frecuencia y severidad de la hemorragia intraventricular y leucomalacia periventricular en neonatos de bajo peso en tres hospitales de Lima, Perú se evaluaron 385 neonatos menores de 2000 g de peso al nacer durante mayo del 2012 a julio del 2014. Se obtuvo ultrasonidos cerebrales a las 40 semanas de gestación, 3-5 días de vida y 3-4 semanas de vida. Hemorragia intraventricular se presentó en 19,2% neonatos con menos de 1500 g y fue severa (grado III o con infarto hemorrágico periventricular) en 9,6% neonatos menores de 1500 g. La mortalidad en neonatos con hemorragia intraventricular fue de 47,1%, se encontró leucomalacia periventricular en 5,4% de los neonatos menores de 1500 g. Ambos diagnósticos fueron más frecuentes en neonatos con menor peso. La frecuencia de hemorragia intraventricular es similar a lo reportado en otros países; sin embargo, la severidad y mortalidad es mayor.

ABSTRACT To describe the frequency and severity of intraventricular hemorrhage and periventricular leukomalacia in low birth-weight neonates in three hospitals in Lima, Peru, 385 newborn babies weighing under 2,000 g at birth were evaluated between May 2012 and July 2014. Brain ultrasounds were obtained at 40 weeks' gestation, 3-5 days of life, and 3-4 weeks of life. Intraventricular hemorrhage occurred in 19.2% of neonates weighing under 1,500 g and was severe (grade III or with periventricular hemorrhagic infarction) in 9.6% of neonates under 1,500 g. Mortality in infants with intraventricular hemorrhage was 47.1%, while periventricular leukomalacia was found in 5.4% of neonates 1,500 g and under; both diagnoses were more frequent in lower-weight babies. The frequency of intraventricular hemorrhage is similar to that reported in other countries; however, severity and mortality are greater.

Mecanismos de lesión cerebral en niños prematuros / Mechanisms of brain injury of the premature baby

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

Fibrodisplasia osificante progresiva plus por una variante patogénica del gen ACVR1: caso clínico / Fibrodysplasia ossificans progressiva: report of one case

Fibrodysplasia ossificans progressiva (FOP) or myositis ossificans, is a genetic disease, with a prevalence of 1 in 2.000.000. It is caused by pathogenic variants in ACVR1 gene and characterized by soft tissue heterotopic ossification, starting in the second decade of life. It is associated to early mortality caused by respiratory complications. It evolves in flare-ups, triggered by soft tissue injuries; therapy is symptomatic, using analgesia, steroids and diphosphonates. We report a 12-year-old female with left renal agenesis, hallux valgus and intellectual disability, presenting with a six months history of thoracic kyphosis, tender nodules in the thorax, and rigidity of right elbow and left knee. Clinical examination revealed dysmorphic facial features. A magnetic resonance showed heterotopic ossification nodules, which was confirmed with spinal radiography. These findings prompted the diagnosis of FOP. Pain treatment was started, and prednisone was used during flare-ups. The ACVR1 gene was analyzed and a pathogenic variant, p. Arg206His, was found, confirming the diagnosis of FOP.

Delayed Extensive White Matter Injury Caused by a Subdural Hemorrhage and Role of Corticospinal Tract Integrity

A subdural hemorrhage (SDH) is a common disorder with usually good prognosis. Most SDHs resolve with or without with minimal sequelae. We present a case report of a patient with SDH, who had delayed extensive white matter injury with disruptions of corticospinal tracts (CSTs) by diffusion tensor imaging (DTI) and showed abysmal prognosis, despite long-term rehabilitation. A 62-year-old man with an SDH underwent burr hole trephination for hematoma removal. Within 7 days, the hemorrhage diminished. At 12 weeks after the onset, the patient's weakness did not improve, and a follow-up magnetic resonance imaging revealed extensive leukomalacia, especially in the white matter. The DTI for CST revealed severe injury of CST integrity. He did not re-gain muscle strength and functional independence, despite 3 months of inpatient rehabilitation. This case describes SDH with delayed extensive white matter injury and exceptional poor prognosis and urges caution in that the SDH may induce very variable functional recovery. Besides, DTI for CST would be useful in predicting the long-term functional prognosis in extensive white matter injury.

Comparison of Clinical Factors and Neurodevelopmental Outcomes between Early- and Late-Onset Periventricular Leukomalacia in Very Low Birth Weight Infants

PURPOSE: To analyze and compare the clinical factors and neurodevelopmental outcomes compare early- and late-onset periventricular leukomalacia (PVL) in very low birth weight infants (VLBWI). METHODS: We performed a retrospective study involving 199 newborn infants weighing < 1,500 g admitted to the neonatal intensive care unit between March 2009 and December 2015. VLBWI with PVL were categorized into early- and late-onset PVL groups based on the time of diagnosis based on 28 days of age. We analyzed the clinical factors and neurodevelopmental outcomes between the groups. RESULTS: The incidence rate of PVL was 10.1% (16/158). The Apgar score at 1 minute and the mean duration of tocolytic therapy were associated with the development of PVL. The incidence rate of premature rupture of membranes (PROM) was significantly higher in the early-onset PVL group (P=0.041). No significant differences were observed in neurodevelopmental outcomes between the early- and late-onset PVL groups. CONCLUSION: Results suggest that a higher incidence of PROM was associated with clinical characteristics in the early-onset PVL group. No significant intergroup differences were observed in neurodevelopmental outcomes; however, the Bayley Scales of Infant Development-III scores were lower in the early-onset PVL group.

Risk Factors for Brain Damage in Preterm Infants After Late-Onset Circulatory Collapse Events

PURPOSE: This study aimed to identify risk factors for brain damage in infants with late-onset circulatory collapse (LCC), a circulatory failure that responds to glucocorticoid therapy. METHODS: We retrospectively reviewed 167 infants (gestational age < 35 weeks) who had hypotension between April 2009 and March 2017 at Boramae Medical Center. Forty infants were diagnosed with LCC and divided into two groups based on ultrasonography and magnetic resonance imaging findings: infants with periventricular leukomalacia (n=9) and those with normal images (n=31) after LCC. The clinical factors of these two groups, including perinatal characteristics, clinical features during the LCC period, and neonatal morbidities, were compared. RESULTS: There were no significant differences in perinatal characteristics and postnatal morbidities between the two groups. Postnatal age was greater in the group with brain damage (16 days vs. 24 days, P=0.047). The lowest mean blood pressure (MBP) and lowest serum sodium concentration were significantly lower in the brain damage group (19 mm Hg vs. 22 mm Hg, P=0.034; 125 mmol/L vs. 129 mmol/L, P=0.043). There were no significant differences in other clinical factors, including cortisol levels, and inotrope and hydrocortisone use. In multivariate logistic regression, older postnatal age (odds ratio [OR], 1.147; P=0.049), lower MBP (OR, 0.616; P=0.031), and lower sodium concentration (OR, 0.728; P=0.037) during the LCC period highly predicted brain damage in infants with LCC (area under the curve 0.882, P=0.001). CONCLUSION: Close monitoring of LCC signs even in long-term stable preterm infants and management for preventing severe hyponatremia and hypotension are important to minimize the occurrence of brain damage in infants with LCC.

Study on the relationship between Toll like receptor 4 expression and apoptosis in periventricular leukomalacia rat model induced by hypoxia-ischemia / 中华实用儿科临床杂志

Objective@#To investigate the correlation between Toll like receptor 4 (TLR4) expression and apoptosis in periventricular leukomalacia (PVL) rat model induced by hypoxia-ischemia.@*Methods@#One hundred and forty three-day-old sprague-dawley (SD) rats, which were divided into experimental group (ischemia-hypo-xia group) and control group (sham operation group) randomly, were used to establish a hypoxic model by ligating the right common carotid artery and inhaling gas mixtures with 60 mL/L oxygen and 940 mL/L nitrogen.The rats were killed 6 h, 12 h, 24 h, 3 d, 7 d after model reproducing and the brain tissues were used for the following experiments.The pathological changes and apoptosis of brain tissues were detected by way of hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel) assay respectively, and TLR4 expression was detected by adopting immunohistochemistry and reverse-transcription polymerase chain reaction(RT-PCR). The data were analyzed by using the SPSS 19.0 software.@*Results@#TLR4 expression in the modeling rat brain commenced to increase in 6 hours (0.541±0.069, 0.166±0.058)and reached the peak in 3 days(1.932±0.161, 0.300±0.039), and then began to decline in 7 days (1.242±0.109, 0.220±0.025) post hypoxia-ischemia.Compared with the control group, there were statistical significances at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The apoptosis of brain ti-ssue cells in the modeling rat brain started to increase at 6 hours(21.33±3.50) and reached the peak in 3 days (35.97±4.20), and then began to decline in 7 days (31.02±4.22) post hypoxia-ischemia.Compared with the control group, there were statistical significance at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The TLR4 expression was positively correlated with cell apoptosis (r=0.774, 0.575, all P<0.05).@*Conclusions@#In the rat model of PVL induced by hypoxia-ischemia, TLR4 is likely to injure the neural cell through apoptosis.

Mechanism of ferroptosis and its role in neurological diseases / 中国药理学通报

Ferroptosis is distinct from apoptosis,autophagy,necrosis,cornification and other cell deaths from morphological,biochemical as well as genetic aspects.Ferroptosis plays a critical role in neurological diseases and cancers.Neurological diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,stroke,periventricular leukomalacia and so on,are characterized by multiple etiologies and mechanisms,and are potentially correlated with ferroptosis.Based on the recent researches on ferroptosis and neurological diseases,this review investigates ferroptosis and its role in neurological diseases.

Cystic periventricular leukomalacia: magnetic resonance imaging changes and motor development outcomes in neonates at different stages after birth / 中国新生儿科杂志

Objective To compare the magnetic resonance imagings (MRI) of neonates diagnosed with cystic periventricular leukomalacia (cPVL) at different stages after birth , and to clarify the relationship of MRI and motor development outcomes.Method Data of neonates admitted to the Shengjing Hospital of China Medical Univerisity from January 2010 to May 2015 diagnosed with cPVL by MRI were studied retrospectively.Subjects were assigned into two groups according to time of diagnosis : early－diagnosed group (≤7 d) and late－diagnosed group (＞7 d).The MRI and subsequent motor development outcome were compared between two groups.Result There were 35 neonates in early－diagnosed group.The cysts were mainly located in the anterior horn of the lateral ventricle (35 infants), the body of the lateral ventricle (2 infants) and the centrum semiovale (1 infants).Only one cyst were found in 17 infants, two cysts in 14 infants, three or more cysts in 4 infants.There were 45 cases in the late－diagnosed group, the cysts were mainly located in the centrum semiovale ( 35 infants ) and the posterior horn of the lateral ventricle (34 infants), the body (20 infants) and the anterior horn (10 infants) of lateral ventricle.Only one cyst were found in 3 infants, two cysts in 5 infants, three or more cysts in 37 infants.Among the 23 infants in the early－diagnosed group with follow－up, 22 infants are clinically normal , one infant with spastic diplegia (4.3%).Among the 24 infants in the late－diagnosed group with followe－up, 4 infants are clinically normal , 20 infants with spastic hemiplegia , diplegia or quadriplegia (83.3%).There are significant differences of incidence of cerebral palsy between the two group (P＜0.05).Conclusion MRI imaging showed that the location, number of cysts are different between the early－diagnosed and late－diagnosed group, and the motor development outcome of the early－diagnosed group are better , which indicates the prognosis of cPVL that occurred in utero are better than acquired cPVL after birth.

Mechanisms of vascular endothelial growth factor receptor 2 expression regulation by erythropoietin in a premature rat model of periventricular white matter damage / 中华围产医学杂志

Objective To explore the mechanisms of vascular endothelial growth factor receptor 2 (VEGFR2) expression regulated by recombinant human erythropoietin (rh-EPO) in a premature rat model of periventricular white matter damage.Methods Sprague-Dawley rats aged three days were randomly divided into five groups:sham group without hypoxia-ischemia (HI),HI group (HI with saline administration),HI+erythropoietin (EPO) group,HI+erythropoietin receptor (EPOR) antagonist group and HI+EPO+EPOR antagonist group.Rat pups were either subjected to permanent ligation of the right common carotid artery and 6％ O2+94％ N2 for two hours (HI) or sham operated and exposed to normal air (sham).After the operation,rats in the HI+EPOR antagonist and HI+EPO+EPOR antagonist groups received a single intraventricular injection of EPOR antagonist (5 μ l).Four hours after the operation,rats in the HI+EPO and HI+EPO+EPOR antagonist groups received a single intraperitoneal injection of rh-EPO (5 U/g).Western-blot was performed to detect EPOR,phosphorylated EPOR (p-EPOR),extracellular regulated protein kinases (ERK) and phosphorylated ERK (p-ERK) at 60 and 90 minutes after the models were established successfully,and also used to analyze the expression of VECFR2 on day 2 and 4.Analysis of variance and SNK test were used as statistical methods.Results At 60 and 90 minutes after model establishment,the expression of EPOR protein in rat brain tissues was increased in HI (1.717±0.206 and 1.416±0.242),HI+EPO (2.557±0.222 and 2.111±0.159) and HI+EPO+EPOR antagonist (1.547±0.170 and 1.452±0.250) groups as compared with that in sham group (1.095±0.182 and 0.751 ±0.136),that in HI+EPO group was higher than that in HI and HI+EPO+EPOR antagonist groups,and that in HI+EPOR antagonist group (1.088±0.160 and 1.020±0.174) was lower than that in HI group.All differences were statistically significant (F=30.154 and 20.265,both P＜0.05).The expressions of p-EPOR,p-ERK and VEGFR2 in the five groups were consistent with the expression of EPOR,and the differences were also statistically significant (all P＜0.05).In addition,the expression of VEGFR2 in HI+EPO+EPOR antagonist group was lower than that in HI group on day 4 (1.053 ± 0.118 vs 1.439± 0.074,F=54.248,P＜0.05).No statistically significant difference in ERK expression was found among all groups at 60 or 90 minutes after modeling (F=1.117 and 0.734,both P＞0.05).Conclusions ERK signaling pathways will be affected by EPO binding to EPOR.As a result,VEGFR2 expression was increased leading to enhanced angiogenesis in a premature rat model of periventricular white matter damage.

Gardnerella vaginalis in perinatology: An overview of the clinicopathological correlation

@#Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1β and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes.

Gardnerella vaginalis in perinatology: An overview of the clinicopathological correlation

@#Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1β and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes.