Reducing neuroinflammation and improving neurobehavioral functions: the protective roles of resveratrol for germinal matrix hemorrhage in neonatal rat model / 中国新生儿科杂志

Objective:To study the roles of resveratrol in reducing neuroinflammation and improving neurobehavioral functions after germinal matrix hemorrhage (GMH) in neonatal rat model.Methods:GMH model was established intraparenchymally injecting bacterial collagenase in 7-day-old SD rats. 108 rats were randomly assigned into 18 groups (6 in each group), including 4 sham groups, GMH (12 h, 24 h, 72 h, 7 d) groups, 3 GMH+vehicle (dimethylsulfoxide, DMSO) groups, 5 GMH+resveratrol (10 mg/kg, 100 mg/kg, 1 000 mg/kg) groups and 2 GMH+resveratrol+EX527 (SIRT1 inhibitor) groups. Negative geotaxis and righting reflex tests were used to evaluate the short-term neurobehavior. Water maze, foot fault and Rotor-Rod tests were used to assess the long-term neurobehavior. Immunofluorescence was used to quantify the IL-1β and MPO positive cells (inflammatory markers) in peri-hematoma area. Western blot was used to evaluate the expression of relevant proteins in the brain.Results:Endogenous sirtuin-1(SIRT1) decreased to the lowest level at 24 h and then increased gradually. Phosphorylated NF-κB increased at 12 h, peaked at 72 h and returned to normal level at 7 d after GMH. Compared with the control group and other doses groups, GMH treated with resveratrol (100 mg/kg) had higher short-term behavioral scores at 48 h and 72 h. Compared with the control group, the resveratrol (100 mg/kg) group also had higher scores in water maze, foot fault and Rotor-Rod tests 22 days later. Immunofluorescence showed less positive IL-1β and MPO cells around hematoma in GMH+resveratrol group than both GMH+vehicle group and GMH+resveratrol+EX527 group. Western blot indicated that IL-1, TNF-α and IL-6 expressions were decreased in GMH+resveratrol group and Ex527 could offset the effects of resveratrol.Conclusions:Resveratrol (optimal dose: 100 mg/kg) can improve the short-term and long-term neurobehavioral functions of neonatal GMH rats. It can reduce GMH cells with positive inflammatory markers around the hematoma, possibly via inhibition of the SIRT1/NF-κB pathway. Resveratrol may be promising for the treatment of GMH patients.

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.

Trans-fontanellar ultrasound evaluation of neonates and infants in a tertiary care hospital in Garhwal referred for sonography

Ultrasound is widely used to diagnose various conditions in neonates and infants like intracranial hemorrhage, hypoxic-ischemic insult, changes of birth asphyxia and congenital disorders of the ain like hydrocephalus, etc as it is easily available, simple and noninvasive and more important is that it lacks ionizing radiation. The present hospital-based study of cranial sonography (Trans-fontanellar ultrasound) done in the Department of Radiodiagnosis, HNB Base government teaching hospital situated in Srinagar Garhwal, was done with the aim of assessing the burden of intracranial disorders in neonates and infants, especially the premature newborns who get admitted in neonatal intensive care units. A retrospective descriptive analysis was done on the data of 196 CUSG done.70.4 % CUSG were performed on neonates, 24.5% were performed on age group 29 days to 6 month age group and rest on age more than 6 months. The male-female gender ratio was 1: 0.96. The most common neonatal pathological conditions were changes of Hypoxic- ischemic encephalopathy (HIE) (28.4 %). Cranial sonography is a useful diagnostic tool in the evaluation of neonatal and infant ain and is a well-established mode of making primary diagnosis.It is preferred because it can be rapidly performed and is a portable, cost-effective test.

Clinical Features of Congenital Cytomegalovirus Infection in Neonates / 대한주산의학회잡지

OBJECTIVE: Cytomegalovirus(CMV) is the most common cause of congenital infection with diverse clinical features according to the age of hosts. This study was done to evaluate clinical manifestations and complications in congenital CMV infection. METHODS: Between October 2000 and September 2001, 10 cases of congenital CMV infection were diagnosed by urine culture within 2 weeks after birth. Demographic data, clinical and laboratory findings were collected from maternal and newborn hospital records. RESULTS: There were 7 males and 3 females. Average gestational age was 38+0 weeks(34+2-41+1), average birth weight was 2462+/-598.2g(1670-3360) and 5 cases were small for gestational age. Average head circumference was 31.9+/-1.8cm(29-34.3). There were 4 cases of microcephaly, 6 cases of petechiae, 3 cases of leukocytopenia, 6 cases of thrombocytopenia. There was no case showing hepatomegaly, hepatic dysfunction, or pathologic jaundice. 4 cases showed physiologic jaundice. IgM level was elevated in 5 out of 9 cases. Polymerase chain reaction(PCR) was positive in 7 cases. All cases showed germinal matrix hemorrhage and septated cysts on cranial ultrasonography. 1 case showed cerebral calcification. 1 case showed bilateral sensorineural hearing loss on brainstem auditory evoked potentials(BAEP). There was no case showing chorioretinitis on fundoscopy. CONCLUSION: There were diverse clinical manifestations in CMV infection in neonates. All cases showed germinal matrix hemorrhage and septated cysts. When we find these findings, we should consider the possibility of CMV infection. One patient developed bilateral sensorineural hearing loss, so its early detection and follow-up might be necessary.

Estudio de factores de riesgo para la hemorragia de la matriz del prematuro / Risk factors for germinal matrix hemorrage in preterm infants

Con el propósito de facilitar el diagnóstico clínico de la hemorragia de la matriz germinal del prematuro, se diseñó un estudio de casos (n: 56) y controles (n: 66) para determinar los factores de riesgo de la madre y del niño; también se buscó asociación entre dichos factores y la gravedad del evento. No se halló relación entre los factores de riesgo maternos y la presencia o gravedad de la hemorragia. En cuanto a los niños, la edad gestacional menor de 31 semanas, el uso de ventilación mecánica y la persistencia del ductus arterioso mostraron una relación estadística con el evento (p < 0.05), mientras que la sumatoria de tres o más riesgos la tuvo con la gravedad del mismo (p < 0.05). Se concluye que los mencionados factores de riesgo pueden ser indicativos del desarrollo de la hemorragia de la matriz germinal en el prematuro

To facilitate clinical diagnosis of germinal matrix hemorrhage In preterm infants, a study of cases {n: 56) and controls {n: 66) was carried out. Association was investigated between hemorrhage and maternal and neonatal risk factors; also included was the correlation between such factors and seriousness of the hemorrhagic episode. No correlation was found between maternal risk factors and hemorrhage or its seriousness. Concerning neonatal risks, gestational age under 31 weeks, the use of mechanical ventilation and persistence of ductus arteriosus, independently, showed statistical correlation with the hemorrhage {p < 0.05), whereas the simultaneous presence of three or more risks correlated with intensity of hemorrhage {p < 0.05). We conclude that the abovementioned neonatal risk factors can be suggestive of the development of germinal matrix hemorrhage in preterm Infants