Vascular endothelial growth factor in neonates with perinatal asphyxia (original) (raw)
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Brain and Development, 2004
Excitatory amino acids, cytokines and nitric oxide (NO) have been studied in the etiology and pathogenesis of hypoxic ischemic encephalopathy (HIE) of the newborn. Vascular endothelial growth factor (VEGF) is a known mediator of angiogenesis and has been shown to induce vascular proliferation and permeability via NO-mediated mechanism during hypoxia. The objective of this study was to investigate the cerebrospinal fluid and serum VEGF and NO levels in different stages of HIE and the correlation between the two mediators. Cerebrospinal fluid (CSF) and serum samples of 19 newborns with HIE and 13 controls were obtained within the first 24 h of life and kept at 2 70 8C until the time of measurement. NO levels were determined by Sievers NOA by chemiluminescence method and VEGF levels were measured by the enzyme-linked immunosorbent assay double sandwich method. The NO levels in CSF were higher than the control and mild HIE group in newborns with moderate to severe HIE, and VEGF levels in CSF were higher in the mild HIE group compared to controls but similar in the moderate to severe HIE group compared to mild HIE and control patients. There was no difference between groups with regard to serum NO or VEGF levels, and no correlation was observed between NO and VEGF levels both in CSF and serum samples. Depending on the severity of the hypoxic insult the stimulus for NO production by VEGF may have variable effects on endothelial cells which may give rise to the current results. q
Objective: Intraventricular haemorrhage (IVH) is a major problem in premature infants. Our objective is to assess the early predictive value of vascular endothelial growth factor (VEGF) for development of IVH and management of its squeal in preterm neonates. Methods: We prospectively studied 150 preterm neonates (PT) less than 34 weeks gestation. Fifty of them completed the study. 30/50 developed IVH during follow up, and 20 did not. First 24 hours, and 3rd day serum samples were collected. Cerebrospinal fluid (CSF) samples were withdrawn for 10 IVH patients. Results: Serum VEGF; both samples were increased in IVH compared to non-IVH group (P = 0.001). PHVD-group (n = 10) had higher VEGF in both samples than resolved IVH (P = 0.004), (P = 0.005). While, VEGF increased in the IVH group 2nd sample compared to 1st (P = 0.000), it decreased in non-IVH group, P = 0.033). Each 1 unit increase in 1ST VEGF increased the risk of occurrence of IVH by 1.6%. 3rd day VEGF at a cut-off value of 135 pg/ml is 96% sensitive and 100% specific to predict PHVD. Serum VEGF inversely correlated with TLC, pH, PO2 and HCO3, and positively correlated with PCo2 and FiO2. Conclusion: Serum VEGF predicts development of IVH and PHVD in PT neonates. Also, high CSF level of VEGF could predict the need for permanent shunt placement.
American Journal of Obstetrics and Gynecology, 2003
We investigated the influence of acute hypoxia on the placental vascular endothelial growth factor system in vitro and in vivo in acute birth asphyxia compared with pregnancies that were complicated by preeclampsia and with healthy control subjects. STUDY DESIGN: Messenger RNA levels for vascular endothelial growth factor, flt-1, and KDR were measured by TaqMan real-time polymerase chain reaction in human placental choriocarcinoma cells (BeWo) that were exposed to hypoxia (1% oxygen, 5% carbon dioxide, 94% nitrogen) and in placental tissue of neonates with birth asphyxia (n = 20), newborn infants of mothers with preeclampsia (n = 20), and gestational age-matched control subjects. Immunhistologically, placental vascular endothelial growth factor protein expression was compared among the groups. RESULTS: In BeWo cells, vascular endothelial growth factor, flt-1 and KDR messenger RNA increased in a time-dependent manner in response to hypoxia. In vivo, vascular endothelial growth factor/β-actin and KDR/β-actin messenger RNA were significantly higher in placental tissue of newborn infants with severe hypoxic-ischemic encephalopathy than with newborn infants with mild or no hypoxic-ischemic encephalopathy and control subjects. In chronic placental hypoxia (preeclampsia), vascular endothelial growth factor and both receptors were found to be up-regulated. Increased placental vascular endothelial growth factor expression was confirmed by immunohistologic examination. CONCLUSION: The vascular endothelial growth factor system is up-regulated in response to placental hypoxia and is assumed to be a potential early indicator of severe birth asphyxia. (Am J Obstet Gynecol 2003;188: 517-23.)
Objective: Given the high proliferative activity of germinal matrix and its direct correlation with hypoxemia, it is necessary to investigate the possible molecular regulation pathways, to understand the existing clinical relationship between the hypoxic- ischemic insult and the biomarkers NF-kB, AKT-3, Parkin, TRK-C and VEGFR-1. Methods: A hundred and eighteen germinal matrix samples of the central nervous system of patients who died in the first 28 days of life were submitted to histological and immunohistochemistry analysis to identify the tissue immunoexpression of those biomarkers related to asphyxia, prematurity, and death events within 24h. Results: A significantly increased tissue immunoexpression of NF-kB, AKT-3 and Parkin was observed in the germinal matrix of preterm infants. In addition, significantly decreased tissue immunoexpression of VEGFR-1 and NF-kB was observed in patients who experienced asphyxia followed by death within 24 hours. Conclusions: The results suggest a direct involvement between the hypoxic-ischemic insult and NF-kB and VEGFR-1 markers since a decreased immunoexpression of these biomarkers was observed in asphyxiated patients. Furthermore, it is suggested that there was not enough time for VEGFR-1 to be transcribed, translated and expressed on the surface of the plasma membrane. This temporality can be observed in the relationship between NF-kB expression and the survival time of individuals who died within 24 hours, suggesting that this factor is essential for the production of VEGFR-1 and, therefore, to carry out the necessary remodeling effect to neovascularize the affected region. Keywords: Germinal matrix; NF-kB; VEGFR-1; Prematurity; Hypoxic-ischemic injury.
Translational Stroke Research, 2012
Episodes of neonatal hypoxia-ischemia (H-I) are strongly associated with cerebral palsy and a wide spectrum of other neurological deficits in children. Two key processes required to repair damaged organs are to amplify the number of precursors capable of regenerating damaged cells and to direct their differentiation towards the cell types that need to be replaced. Since hypoxia induces vascular endothelial growth factor (VEGF) production, it is logical to predict that VEGFs are key mediators of tissue repair after H-I injury. The goal of this study was to test the hypothesis that certain VEGF isoforms increase during recovery from neonatal H-I and that they would differentially affect the proliferation and differentiation of subventricular zone (SVZ) progenitors. During the acute recovery period from H-I both VEGF-A and VEGF-C were transiently induced in the SVZ, which correlated with an increase in SVZ blood vessel diameter. These growth factors were produced by glial progenitors, astrocytes and to a lesser extent, microglia. VEGF-A promoted the production of astrocytes from SVZ glial progenitors while VEGF-C stimulated the proliferation of both early and late oligodendrocyte progenitors, which was abolished by blocking the VEGFR-3. Altogether, these results provide new insights into the signals that coordinate the reactive responses of the progenitors in the SVZ to neonatal H-I. Our studies further suggest that therapeutics that extend VEGF-C production and/or agonists that stimulate the VEGFR-3 will promote oligodendrocyte progenitor cell development to enhance myelination after perinatal brain injury.
Biochemical and clinical predictors of hypoxic-ischemic encephalopathy after perinatal asphyxia
Objective: To determine the usefulness of measures, available shortly after birth, as predictors of hypoxic-ischemic encephalopathy (HIE) following perinatal asphyxia. Patients: All inborn patients at Southmead Hospital between January 2012 and March 2014 at 36 weeks gestation with a pH <7 or BE >16 on cord or baby's blood within one hour of birth or 10-minute Apgar score 5 or requiring intermittent positive pressure ventilation at 10 minutes were eligible for inclusion. Methods: ROC curves were derived for the perinatal clinical and biochemical measures to establish their predictive values for the development of HIE and the area under the curve (AUC) used as the measure of prediction. Results: We identified 79 eligible babies. Infants qualifying for therapeutic hypothermia (TH) based on aEEG abnormalities were considered to have HIE (n ¼ 13; 16.5%), whereas babies with normal aEEG were classified as "non-HIE" (n ¼ 66; 83.5%). The highest AUC measure was associated with the five-minute Apgar score (0.89 (0.79-0.99)). Troponin T (0.81 (0.64-0.98)) and ALT (0.78 (0.60-96)) also showed high values. Conclusions: In this work, the Apgar score, troponin T and ALT were found to be strong and useful predictors of HIE.
Experimental and Therapeutic Medicine, 2021
Perinatal hypoxic-ischemic encephalopathy (HIE) represents a major cause of neonatal death or long-term disability. Inflammation plays an important role in mediating brain damage induced by neonatal hypoxic-ischemic encephalopathy. The mechanisms underlying the inflammatory response in hypoxia and ischemia are complex and are still being extensively researched. The objective of this study was to determine the predictive value of peak lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin (PCT) and of the evolution of leukocytes, neutrophils and lymphocytes in the first 96 h after birth for the grade of encephalopathy and neurodevelopmental outcome in newborns with HIE. In order to reveal this relationship we used comparisons between the above mention parameters. The observed hematological changes were nonspecific. The vast majority of the 78 newborns included in the study had PCT values above normal in the first 24 h, contrasting with CRP values that were positive in only 15.8% of the patients. A total of 76.9% of the patients had LDH values higher than the upper limit of normal values. The mean LDH values in patients with an unfavorable prognosis were 1,235 U/l. We can conclude that LDH is a good predictor of HIE in the first 12/24 h after birth.
Vascular endothelial growth factor in preterm infants with respiratory distress syndrome
Pediatric Pulmonology, 2005
Respiratory distress syndrome (RDS) secondary to surfactant deficiency is a common cause of morbidity and mortality in premature infants. Increasing evidence suggests that vascular endothelial growth factor (VEGF) may contribute to surfactant secretion and pulmonary maturation. However, differences in cord blood VEGF concentrations in infants with and without respiratory distress syndrome have not been reported. We hypothesized that premature infants with higher VEGF levels in cord blood had a lower risk of developing RDS. Cord blood samples were obtained from preterm infants born at 32 weeks of gestation or earlier. Infants were excluded if there was evidence of prenatal maternal infection or any infection within the first 3 days of life. Cord blood VEGF levels were measured using an enzyme-linked immunosorbent assay (ELISA). We found that neonates with clinically diagnosed RDS had a lower gestational age (GA), lower birth weight (BW), higher incidence of mechanical ventilation requirements, longer duration of mechanical ventilation, and lower Apgar scores at 1 and 5 min. Infants with RDS had significantly lower cord blood VEGF levels. GA, BW, premature rupture of membranes (PROM), and antenatal steroid treatment were not associated with changes in cord blood VEGF levels. The specificity of cord blood VEGF above 34 pg/ml for predicting the absence of RDS was 86%, the sensitivity was 53%, the positive predictive value was 84%, and the negative predictive value was 56%. Our data demonstrated that cord blood VEGF elevation was significantly correlated with an absence of RDS.
Archives of Disease in Childhood, 2012
Background and Aims Neonatal hypoglycemia is a frequent event in small for gestational age (SGA) term newborns. Its clinical significance is a highly controversial issue but in experimental models, hypoglycemia has been reported to cause oxidative stress. Among the reactive species, peroxynitrite is responsible for protein nitration, lipid peroxydation and DNA damage, a process referred to as nitro-oxidative stress which can induce apoptosis. The aim of the present study was to investigate whether hypoglycemia is associated with plasma albumin nitration as a marker of nitro-oxidative stress in SGA term newborns. Methods Using a highly sensitive ELISA we quantified plasma nitroalbumin (PNA) as a marker of peroxynitrite generation in 26 SGA term newborns with close glucose monitoring. We compared PNA concentrations in 9 normoglycemic (glycemia ≥2.5mmol/L) newborns and in 17 hypoglycemic (glycemia < 2.5 mmol/L) newborns. Results PNA measured during the first hours of life was inversely correlated with glycemia (r=-0.63, p=0.01) and significantly higher in hypoglycemic compared to normoglycemic patients (7.4ng/mL [5.0-7.9] in normoglycemic patients vs. 20.8ng/mL [9.9-77.7] in hypoglycemic patients, n=14, p<0.01). PNA measured at day 1 of life was significantly higher in patients with recurrent hypoglycemia compared to patients with transient hypoglycemia and normoglycemic patients. We observed significant correlations between PNA at day 1 and the area under the curve of the glycemia measured before PNA sampling for several threshold values of glycemia. Conclusions These results indicate that recurrent hypoglycemia is associated with systemic protein nitration in SGA term newborns, suggestive of a significant nitro-oxidative stress.