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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present a two-component model of brain white matter damage in preterm neonates. The insult component comprises infection and hypoxia-ischemia, which are both associated with inflammation-related abnormalities in the white matter. The developmental component comprises at least three factors, ie, immaturity of the ependymal/endothelial, oligodendroglial, and endogenous protection systems. All three factors are likely contributors to an increased vulnerability of the preterm newborn's white matter. In this article, we focus on recent developments in oligodendrocyte biology that support the view of certain cytokines and growth factors as oligotrophins based on their capability to enhance oligodendrocyte development or survival. We suggest that research into networks of developmentally regulated endogenous protectors (such as oligotrophins) is necessary to broaden our perspectives in brain injury prevention in preterm newborns.
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PMID:Brain damage in preterm newborns: might enhancement of developmentally regulated endogenous protection open a door for prevention? 1046 83

The neonatal brain appears to be selectively vulnerable to oxidative stress. Several potential mechanisms associated with altered reactive oxygen species metabolism would explain the increased susceptibility. They include increased accumulation of hydrogen peroxide with subsequent neurotoxicity. This enhanced neurotoxicity from H2O2 accumulation may be related to inadequate scavenging abilities of the immature nervous system, such as lower glutathione peroxidase activity. Contributing to the immaturity of the scavenging enzymes is the inability of the developing nervous system to maintain glutathione stores. The immature nervous system is rich in iron, and has more free iron than the mature nervous system. As H2O2 accumulates because of these improper defense mechanisms, it is exposed to this free iron. This exposure results in the generation of OH radical (Fenton reaction), a more potent free radical that can cause severe damage. The rapid conversion of H2O2 to OH in the setting of free iron sets up the immature nervous system for increased cytotoxicity. Understanding the molecular mechanisms of oxidative stress will lead to better therapies for neonatal hypoxia-ischemia.
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PMID:Oxidant mechanisms in neonatal hypoxia-ischemia. 1159 20

The concept that fetal tissue transplants enjoy an immunologic privilege grounds on the primary immaturity of major histocompatibility complex (MHC) expression. However, experiences in human organ transplantation reveal that the immunogenicity of any graft could be modified by external factors such as ischemia. Consequently, the question arises, whether the process of transplantation modifies the immunogenicity of fetal grafts. In a syngeneic rat model (Lewis), fetal adrenal glands were transplanted into the greater omentum of adult hosts. After harvesting the grafts sequentially, the immunogenicity was evaluated by analyzing the expression and distribution of the MHC classes I and II and were compared with untreated organs of equivalent age. The untreated fetal adrenal gland depicted little immunogenicity. However, compared with age-matched untreated control organs, at 2 wk after transplantation, the grafts demonstrated an increased expression of MHC I and II, upregulated throughout the entire adrenal cortex. No signs of MHC-mediated rejection were found. The upregulation of MHC persisted until the eighth week after transplantation. At 3 months after transplantation the expression of MHC I and II returned to the normal pattern of untreated controls. As this study used a purely syngeneic model, the immunologic changes observed could not be induced by a graft vs. host incompatibility, instead they were caused by experimental factors. The expressions of MHC class I and II was increased at 2 wk, but these proteins did not induce a T-cell mediated rejection or cellular infiltration. In conclusion, these findings question the concept of an immunologic privilege of fetal tissue transplants. Instead, experimental factors may modify the tissue's primary immaturity of its MHC. Further investigations must evaluate, whether the increase in MHC expression will have an impact on the rejection of fetal adrenal grafts in allogeneic hosts.
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PMID:Does the transplantation process modify the immunogenicity of fetal adrenal grafts in rat? 1275 46

Doppler parameters enable noninvasive and direct detection of placental insufficiency and brain sparing effect, which occurs as an adaptive mechanism to chronic hypoxemia. It is of great interest if further changes of Doppler parameters, which occur after the detection of the first pathologic value, can anticipate a moment of fetal distress. We investigated growth-restricted fetuses with the brain sparing effect in the time interval between the detection of blood flow redistribution until the distress. The aim of our study was to evaluate longitudinally Doppler parameters in umbilical (Aum), medial cerebral (MCA), renal (AR) and femoral (AF) artery, and find: 1) if there are significant changes in their value; 2) the character and time interval of these changes; and 3) if they differ from changes in biophysical profile (BFP). Prospective clinical study evaluated 35 pregnancies with fetal growth restriction. Fetuses were selected for the study if: 1) there were pathologic cerebral/umbilical (C/U) ratio, 2) at least four Doppler examinations in 3-4 days interval were performed and 3) prepartal fetal distress, defined as silent fetal heart rate pattern with spontaneous and late decelerations, was present. In 28 neonates after delivery umbilical artery gas and acid-base status was determined. Blood flow velocity waveforms were evaluated in Aum, MCA, AR, and AF. Arterial blood flow was estimated by pulsatility index (Pi), while in Aum we also used: present end-diastolic velocity (PEDV), absent end-diastolic velocity (AEDV) and reverse end-diastolic velocity (REDV). All of the fetuses were monitored by cardiotocogram (CTG) once to twice a day and by BFP twice a week. Elective Cesarean section was done in the presence of distress, except if severe immaturity or extreme malnutrition occurred. Etiological factors of placental insufficiency were: 1) hypertensive syndrome (n = 26), 2) chronic renal disease (n = 3), 3) primary antiphospholipid syndrome (n = 2), 4) diabetes mellitus (n = 1), 5) cardiac disease (n = 1) and 6) unknown (n = 2). Initial Doppler examination, with the detection of pathological C/U, was done in time interval between 26. to 32. weeks of gestation (wg) (29.4 +/- 2.5); delivery was between 29. to 34. wg (32.2 +/- 1.9); and average body weight was 1327 +/- 245 g. Pathological BFP was registered in 91.4% of fetuses. Cesarian section has not been done, in spite of distress, in two fetuses (5.7%) due to their extreme immaturity and/or malnutrition, so they died "in utero". Hypoxemia was registered in 96.4% (27/28) neonates, while acidosis in 71.4% (20/28). Neonatal morbidity was 93.9% (31/33), neonatal mortality 8.6%, while perinatal mortality was 14.3%. We found high significant difference (P < 0.001) in Pi Aum, Pi ACM and Pi AR in the time interval between the detection of pathological C/U ratio and fetal distress, while the difference was insignificant for the values of Pi AF (table). The value changes are characterized by: continuing increase of Pi Aum, with a maximum in the last week before the distress; biphasic character of PI MCA--tendency to decrease in the first two and significant increase in the last week; and significant increase of Pi AR one and a half week before the distress (table, graphic). Three weeks before the distress in 7 (53.8%) cases we registered PEDV, in 6 (46.2%) AEDV, while we didn't register REDV in any case. In the last week there were 3 (8.6%) PEDV, 23 (65.7%) AEDV and 9 (25.7%) REDV. Significant changes in Doppler parameters suggest that even after the blood redistribution in growth restricted hypoxemic fetuses further haemodynamic changes occur. Preterminal increase in Pi Aum can be due to: 1) release of leucotrien, tromboxan and free oxygen radicals and consecutive vasoconstriction in villous arteries; 2) increase of diastolic arterial pressure as a result of hypoxic-ischemic central nervous system (CNS) insult; 3) decreased combined heart minute volume in preterminal phase of hypoxemia. The increase of Pi MCA values is a result of hypoxic-ischemic CNS insult. As a consequence of hypoxia ischemia occurs by two mechanisms: local vasodilatatory agents production decrease, or due to the brain edema. The increase of Pi AR values can be explained by severe hypoxemia with the failure of local autoregulation of renal blood flow. The greatest changes in BFP values were registered in the first half, while in Doppler parameters in the second half of the studied interval suggesting that Doppler parameters more accurately announce fetal distress. We can conclude the following: 1) fetal distress appears after the presence hypoxic-ischemic CNS insult, and therefore late when sequels are concerned; 2) if the fetus is mature, elective delivery should be planed after the appearance of pathological C/U ratio, or with the pathological BFP at the latest, in order to avoid post-hypoxic sequels; 3) if the fetus is immature, pregnancy can be prolonged safely, in spite of pathological C/U ratio and BFP, with intensive monitoring of Doppler parameters until the detection of their increased values.
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PMID:[Longitudinal analysis of arterial Doppler parameters in growth retarded fetuses]. 1460 57

Premature birth can have devastating effects on brain development and long-term functional outcome. Rates of psychiatric illness and learning difficulties are high, and intelligence on average is lower than population means. Brain imaging studies of infants born prematurely have demonstrated reduced volumes of parietal and sensorimotor cortical gray matter regions. Studies of school-aged children have demonstrated reduced volumes of these same regions, as well as in temporal and premotor regions, in both gray and white matter. The degrees of these anatomical abnormalities have been shown to correlate with cognitive outcome and with the degree of fetal immaturity at birth. Functional imaging studies have shown that these anatomical abnormalities are associated with severe disturbances in the organization and use of neural systems subserving language, particularly for school-aged children who have low verbal IQs. Animal models suggest that hypoxia-ischemia may be responsible at least in part for some of the anatomical and functional abnormalities. Increasing evidence suggests that a host of mediators for hypoxic-ischemic insults likely contribute to the disturbances in brain development in preterm infants, including increased apoptosis, free-radical formation, glutamatergic excitotoxicity, and alterations in the expression of a large number of genes that regulate brain maturation, particularly those involved in the development of postsynaptic neurons and the stabilization of synapses. The collaboration of both basic neuroscientists and clinical researchers is needed to understand how normal brain development is derailed by preterm birth and to develop effective prevention and early interventions for these often devastating conditions.
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PMID:Brain imaging studies of the anatomical and functional consequences of preterm birth for human brain development. 1499 87

The blood-brain barrier (BBB) is a diffusion barrier, which impedes influx of most compounds from blood to brain. Three cellular elements of the brain microvasculature compose the BBB-endothelial cells, astrocyte end-feet, and pericytes (PCs). Tight junctions (TJs), present between the cerebral endothelial cells, form a diffusion barrier, which selectively excludes most blood-borne substances from entering the brain. Astrocytic end-feet tightly ensheath the vessel wall and appear to be critical for the induction and maintenance of the TJ barrier, but astrocytes are not believed to have a barrier function in the mammalian brain. Dysfunction of the BBB, for example, impairment of the TJ seal, complicates a number of neurologic diseases including stroke and neuroinflammatory disorders. We review here the recent developments in our understanding of the BBB and the role of the BBB dysfunction in CNS disease. We have focused on intraventricular hemorrhage (IVH) in premature infants, which may involve dysfunction of the TJ seal as well as immaturity of the BBB in the germinal matrix (GM). A paucity of TJs or PCs, coupled with incomplete coverage of blood vessels by astrocyte end-feet, may account for the fragility of blood vessels in the GM of premature infants. Finally, this review describes the pathogenesis of increased BBB permeability in hypoxia-ischemia and inflammatory mechanisms involving the BBB in septic encephalopathy, HIV-induced dementia, multiple sclerosis, and Alzheimer disease.
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PMID:The blood-brain barrier: an overview: structure, regulation, and clinical implications. 1520 56

Following metabolic size allometry, the specific metabolic rate of mammals increases with decreasing body mass, resulting in a steeper metabolic fall-off and a faster exhaustion of energy reserves under hypoxic conditions. However, both mammalian hibernators and fetuses are able to temporarily "switch-off" Kleiber's rule as an adaptation to limited food or oxygen supply. Further exceptions to the usual metabolic size relationship are observed in newborn mammals. For instance, neonatal mouse hearts exhibit slower calorimetric "dying curves" under conditions of ischemia, although their aerobic tissue metabolic rates are higher than in adult samples. This is apparently due to a transient reduction of metabolic rate back to the former feto-maternal level. A continuing deviation from metabolic size allometry is found in newborn marsupials (Monodelphis domestica) where the "inappropriately" low specific metabolic rate is a precondition of efficient growth and tissue aerobiosis in spite of extreme immaturity. Obviously, adaptive suppression of elevated metabolism in organisms of small size results in a dramatic improvement of oxygen supply. Vice-versa, the overall increase in specific metabolic rate with decreasing body size might be regarded as one of several phylogenetic adaptations to protect tissues from hyperoxygenation.
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PMID:Metabolic adaptation to hypoxia: cost and benefit of being small. 1528 95

Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia; PVL) and diffuses myelination disturbances. Recent neuroimaging studies support that the incidence of PVL is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. Factors that predispose to PVL during prematurity include hypoxia, ischemia, and maternal-fetal infection. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary, but not sufficient to generate PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin-forming oligodendrocytes. Chemical mediators that may contribute to white-matter injury include reactive oxygen species glutamate, cytokines, and adenosine. As our understanding of the pathogenesis of PWMI improves, it is anticipated that new strategies for directly preventing brain injury in premature infants will develop.
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PMID:Perinatal white matter injury: the changing spectrum of pathology and emerging insights into pathogenetic mechanisms. 1680 10

Impaired microcirculation with evolving sludge phenomenon and thrombosis underlie placental changes in maternal thyroid disease. Capillary blood circulatory defect is largely due to villous immaturity. Placental tissue ischemia gives rise to fibrinoid, sclerosis, and alternative processes. Dysadaptive changes are mostly observed in thyrotoxicosis and hypothyroidism. Adaptive processes evolving at the ultrastructural level are best pronounced in euthyroid goiter.
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PMID:[Impact of maternal thyroid disease on the formation of relationships in the maternal-placental-fetal system]. 1698 91

Survivors of premature birth have a predilection for perinatal brain injury, especially to periventricular cerebral white matter. Periventricular white matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia) and diffuse myelination disturbances. Recent neuroimaging studies support that the incidence of periventricular leukomalacia is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary but not sufficient to generate the initial injury that leads to PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin-forming oligodendrocytes. There has been substantial recent progress in the understanding of the cellular and molecular pathogenesis of PWMI. The oligodendrocyte progenitor is a key target for preventive strategies to reduce ischemic cerebral white matter injury in premature infants.
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PMID:Maturation-dependent vulnerability of perinatal white matter in premature birth. 1726 26


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