摘要:

To evaluate the hypothesis that the proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor-α might be the link between prenatal intrauterine infection (IUI) and neonatal brain damage, the authors review the relevant epidemiologic and cytokine literature. Maternal IUI appears to increase the risk of preterm delivery, which in turn is associated with an increased risk of intraventricular hemorrhage, neonatal white matter damage, and subsequent cerebral palsy. IL-1, IL-6, and TNF-α have been found associated with IUI, preterm birth, neonatal infections, and neonatal brain damage. Unifying models not only postulate the presence of cytokines in the three relevant maternal/fetal compartments (uterus, fetal circulation, and fetal brain) and the ability of the cytokines to cross boundaries (placenta and blood-brain barrier) between these compartments, but also postulate how proinflammatory cytokines might lead to IVH and neonatal white matter damage during prenatal maternal infection. Interrupting the proinflammatory cytokine cascade might prevent later disability in those born near the end of the second trimester.Abbreviations: BBB,blood-brain barrier;IUI,intrauterine infection;IVH,intraventricular hemorrhage;PVL,periventricular leukomalacia;TNF,tumor necrosis factor;VLBW,very low birth weight

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This study was made to determine the life span of adult red cells transfused to early preterm infants. Nineteen very preterm infants (birth weight, 878.7 ± 221 g; gestational age, 26.8 ± 1.5 wk at birth) were sampled weekly after their last blood transfusion to determine the level(%) of fetal Hb in their circulation. Two microliters of blood were subjected to reverse phase HPLC to separate the α, β, and γ globin components of their Hbs. The percent of fetal Hb (HbF) was calculated asγ/γ + β × 100. The life span of the adult erythrocytes transfused was defined as the time interval between the transfusion and when the percentage of HbF in the recipient's circulation returns to the HbF levels that exist in the infant's autologous red cells (the maximum post transfusion HbF level). Twelve of the 19 infants were followed until their autologus HbF levels were reached. Their mean adult red blood cell life span was 56.4± 7 d (range: 46-68 d). The results obtained in this study imply that the number of days after a transfusion at which half the cells infused remain in the circulation in a preterm infant is about 30 d.Abbreviations: HbF,fetal Hb;HbA,adult Hb

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Patients with tetralogy of Fallot may have episodes of paroxysmal hypoxic spells (“tet spells”) or could be asymptomatic. In patients who have these episodes, treatment with a β-adrenoceptor (βAR) blocking agent can often ameliorate or attenuate the severity of the symptoms. Additionally, excitement, crying, and situations associated with increased sympathetic activity could provoke the occurrence of these hypoxic spells. We hypothesized that altered myocardial βAR function may contribute to the development of paroxysmal hypoxic spells in the symptomatic tetralogy patient. Surgically excised right ventricular infundibular myocardial specimens from symptomatic (patients with spells) and asymptomatic patients were used to determine total β1and β2βAR density andβAR adenylyl cyclase activity. Symptomatic patients had a significantly greater number of total βAR. The relative proportion of β1and β2receptors was comparable in both patient groups.βAR-stimulated adenylyl cyclase activity was found to be more enhanced in the symptomatic patient group. Our results indicate that infundibularβARs may play a role in the development of paroxysmal hypoxic spells.Abbreviations: βAR,β-adrenoceptor;CPB,cardiopulmonary bypass;GTP,guanosine triphosphate;ICYP,iodocyanopindolol

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Intraischemic reduction in temperature of 2-3 °C (modest hypothermia) has been demonstrated to provide partial neuroprotection in neonatal animals. This investigation determined if modest hypothermia initiated immediately after brain ischemia provides neuroprotection. Piglets were studied with rectal temperature maintained during the 1st h after 15 min of brain ischemia at either 38.3 ± 0.3 °C (normothermia,n= 11) or at 35.8± 0.5 °C (modest hypothermia,n= 11). The severity of brain ischemia was similar between groups as indicated by equivalent reduction in mean blood pressure (90 ± 15 to 24 ± 3versus92± 13 to 26 ± 3 mm Hg), and changes in cerebral metabolites and intracellular pH (pHi) measured by magnetic resonance spectroscopy(β-nucleoside triphosphate = 44 ± 9versus42 ± 18% of control, control = 100%, pHi: 6.25±.15versus6.24 ± 0.22 for normothermic and modestly hypothermic groups, respectively). In the first 90 min after ischemia, there were no differences between groups in the duration and extent of brain acidosis, and relative concentrations of phosphorylated metabolites. Categorical assessment of neurobehavior was evaluated at 72 h postischemia (n= 16), or earlier if an animal's condition deteriorated (n= 6). Postischemic hypothermia was associated with less severe stages of encephalopathy compared with normothermia (p= 0.05). Histologic neuronal injury was assessed categorically in 16 brain regions, and postischemic hypothermia resulted in less neuronal injury in temporal (p= 0.024) and occipital (p= 0.044) cortex at 10 mm beneath the cortical surface, and in the basal ganglia (p= 0.038) compared with that in normothermia. Modest hypothermia for 1 h immediately after brain ischemia provides partial neuroprotection and may represent an adjunct to resuscitative strategies.Abbreviations: MABP,mean arterial blood pressure;MR,magnetic resonance;pHi, intracellular pH;PCr,phosphocreatine;Pi, inorganic phosphorus;NTP,nucleoside triphosphate;OPS,overall performance score

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We previously have demonstrated that hypocapnia aggravates and hypercapnia protects the immature rat from hypoxicischemic brain damage. To ascertain cerebral blood flow (CBF) and metabolic correlates, 7-d postnatal rats were subjected to hypoxia-ischemia during which they were rendered either hypo-(3.5 kPa), normo- (5.1 kPa), or hypercapnic (7.3 kPa) by the inhalation of either 0, 3, or 6% CO2, 8% O2, balance N2. CBF during hypoxia-ischemia was better preserved in the normo- and hypercapnic rat pups; these animals also exhibited a stimulation of cerebral glucose utilization. Brain glucose concentrations were higher and lactate lower in the normo- and hypercapnic animals, indicating that glucose was consumed oxidatively in these groups rather than by anaerobic glycolysis, as apparently occurred in the hypocapnic animals. ATP and phosphocreatine were better preserved in the normo- and hypercapnic rats compared with the hypocapnic animals. Cerebrospinal fluid glutamate, as a reflection of the brain extracellular fluid concentration, was lowest in the hypercapnic rats at 2 h of hypoxia-ischemia. The data indicate that during hypoxia-ischemia in the immature rat, CBF is better preserved during normo- and hypercapnia; the greater oxygen delivery promotes cerebral glucose utilization and oxidative metabolism for optimal maintenance of tissue high energy phosphate reserves. An inhibition of glutamate secretion into the synaptic cleft and its attenuation ofN-methyl-D-aspartate receptor activation would further protect the hypercapnic animal from hypoxic-ischemic brain damage.Abbreviations: PCr,phosphocreatine;NMDA,N-methyl-D-aspartate;CBF,cerebral blood flow;CSF,cerebrospinal fluid;CGU,cerebral glucose utilization;pHi, intracellular pH;2-DG,2-deoxy-[14C]glucose

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The study evaluates the long-term effect of neonatal hypoxia on the neurochemical activity of the sympathoadrenal system in the rat. One-day-old male pups were exposed to hypoxia (10% O2) for 6 d and thereafter reared under normoxia. Neonatal hypoxia reduced the body weight of 3- and 8-wk-old rats and did not change the blood pressure at 6 wk of age. In sympathetic ganglia, the content and/or turnover rates of norepinephrine were reduced in neonatal-hypoxic rats of 3 and 8 wk of age, but the content and turnover rates of dopamine were unaltered. The effect was not dependent on the type of ganglion. In the superior cervical ganglion, neonatal hypoxia had a selective effect on the type of catecholamine (dopamineversusnorepinephrine), thus suggesting a selective-altered maturation of noradrenergic neurons, but presumably not of the dopaminergic small, intensely fluorescent cells. A long-term deficiency in adrenal activity was the consequence of neonatal hypoxia, as shown by the decrease in the content and turnover rate of dopamine. Neonatal hypoxia elicited a long-term decrease in the content and turnover rates of norepinephrine in heart and lungs but failed to induce a significant effect in kidneys. However, this effect was not tissue-specific. Data provide evidence that a hypoxic episode occurring during a critical period of development in the rat induces a long lasting decrease in the neurochemical activity of the sympathoadrenal system. These results are discussed in terms of their implications for human pathology.Abbreviations: AMPT,α-methyl-p-tyrosine;ANOVA,analysis of variance;PLSD,protected least square difference;SIDS,sudden infant death syndrome;SIF,small, intensely fluorescent

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Fetal alcohol syndrome is one of the leading causes of mental retardation in the United States, but the pathogenesis of the associated brain damage is unknown. We tested the hypothesis that neonatal cerebrovascular responses to CO2and/or hypoxia may be altered by moderate chronic maternal ethanol exposure early in gestation. We studied 26 newborn lambs (1-4 d old). Their mothers had received daily i.v. infusions of either ethanol (1 g/kg; ethanol concentration = 167 ± 3 mg/dL; mean ± SEM) or a similar volume of saline for 3 wk during the first trimester. In nine lambs, we studied cerebral responses to CO2(saline,n= 4; ethanol,n= 5) and in 17 lambs, cerebral responses to hypoxia (saline,n= 7; ethanol,n= 10). Cerebrovascular responses to CO2were not different between the groups. However, the cerebral vasodilatory response to hypoxemia was significantly attenuated in the ethanol lambs, such that cerebral O2delivery was not maintained. During severe hypoxia (arterial Po2= 30 mm Hg), cerebral blood flow increased 106± 23% (mean ± SEM) above baseline in the saline-treated group, but increased only 32 ± 15% above baseline in the ethanol-treated group(p< 0.02). Similarly, cerebrovascular resistance in the saline group decreased 52 ± 6% from baseline, but decreased only 16 ± 11% in the ethanol group (p< 0.02). We conclude that moderate maternal ethanol infusion early in pregnancy attenuates neonatal hypoxic, but not CO2, cerebrovascular responsivity.Abbreviations: CBF,cerebral blood flow;CVR,cerebrovascular resistance;Cao2, arterial oxygen content;CMRo2, cerebral oxygen consumption;OD,cerebral oxygen delivery;MAP,mean arterial blood pressure;Paco2, partial pressure of arterial CO2;Pao2, partial pressure of arterial O2

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The role of adenosine in the modulation of respiration-related neurons was examined using anin vitrobrainstem-spinal cord preparation from neonatal rats (0-4 d old). Respiratory activity was recorded from the C4 or C5 ventral roots by suction electrodes and from inspiratory related neurons (I neurons) in the rostral ventrolateral medulla by microelectrodes. The following substances were added to the preparation superfusate, and their effect was evaluated: the adenosine A1receptor agonistN6-(2-phenylisopropyl)adenosine, R(-)isomer (R-PIA), the adenosine uptake blocker dipyridamole, the adenosine receptor antagonist theophylline, and the specific A1receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). R-PIA and dipyridamole decreased the activity of I neurons and the C4 respiratory burst rate. Furthermore, these compounds induced a significantly more irregular respiratory rate in three-quarters of preparations from the youngest animals (<48 h old) compared with that of controls. Theophylline or DPCPX reversed the effects of both R-PIA and dipyridamole on respiratory rate, regularity of respiratory rate, inspiratory time, amplitude, and intra-burst frequency of I neurons. Thus, adenosine depresses both the I neurons in the rostral ventrolateral medulla and the respiratory motor output. This depression of I neurons and respiratory rate can be abolished by theophylline primarily through a blockade of medullary adenosine A1receptors. An age-dependent correlation of the effects of R-PIA and dipyridamole, with a more pronounced decrease in respiratory activity in preparations from younger animals, indicates that adenosinergic modulation of medullary respiration-related neurons changes during the first days of postnatal life.Abbreviations: R-PIA,N6-(2-phenylisopropyl)adenosine, R(-)isomer;DPCPX,8-cyclopentyl-1,3-dipropylxanthine;RR,respiratory rate (bursts/min);Int. C4,integrated C4/C5 activity;I neuron,inspiratory neuronal unit;fi, intraburst firing frequency of I neuron (spikes/s);Ti, inspiratory time;CV,coefficient of variation;NMDA,N-methyl-D-aspartate

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Secondary brain damage after transient cerebral hypoxiaischemia (HI) is caused by a cascade of cellular events. In this study, complementary methods of magnetic resonance imaging and histochemistry were used to investigate the formation of cytotoxic and vasogenic edema during secondary brain damage induced by transient HI in 7-d-old rats. To elicit injury, 21 rats underwent right common carotid artery ligation followed by 1.5 h of 8% O2exposure. Sequential apparent diffusion coefficient (ADC) and transversal relaxation time (T2) weighted magnetic resonance imaging were recorded for up to 3 d in 13 7-d-old rats. Eight animals were killed at various intervals between the end of HI and 21 h of recovery to perform histochemical assays using neuronal and astrocytic markers. Changes of the ADC revealed a biphasic function for the evolution of cytotoxic edema during the recovery period. At the end of HI, the ADC in the ipsilateral cortex was significantly decreased. Upon reoxygenation, it returned transiently to normal followed by a secondary, although less pronounced, decline after 8-48 h. After this, the ADC rose steadily. From 8 h of recovery, the proportion of vasogenic edema steadily increased as indicated by the T2prolongation. At 21 h, the majority of glial cells showed immunoreactivity for glial fibrillary acidic protein and were of larger size, whereas the neurons were apoptotic. These results indicate that the delayed cerebral injury is accompanied by late glial swelling in conjunction with an enlarged interstitial space due to cell damage.Abbreviations: ADC,apparent diffusion coefficient;CCA,common carotid artery;DWI,diffusion weighted imaging;GFAP,glial fibrillary acidic protein;HI,hypoxia-ischemia;MRI,magnetic resonance imaging;RARE,rapid acquisition with relaxation enhancement;ROI,region of interest;T2, transversal relaxation time;T2WI,T2weighted imaging;TE, time to echo;TR, time to repeat;TUNEL,terminal deoxynucleotidyl transferase dUTP nick end labeling

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Little is known about the antioxidant capacity and oxidant-generating potential of newborn muscle, or how these properties compare with the adult and relate to fatigue resistance. We determined the 1) antioxidant enzyme activities [superoxide dismutase (SOD), catalase, glutathione peroxidase], 2) glutathione content, 3) oxidative capacity [indexed by succinic dehydrogenase activity], 4) extracellular cytochromecreduction, and 5) efficacy of exogenously administered SOD in ameliorating fatiguein vitroof newborn and adult diaphragm (DIA). Newborn and adult DIA SOD activities were not different, whereas newborn catalase activity was greater, and newborn glutathione peroxidase activity and glutathione content less than adult DIA. Succinic dehydrogenase activity was ≈ 2-fold greater in the adult compared with the neonate. Repetitive contractions led to a significant deline in newborn and adult DIA force; this decline was greater in the adult (78± 4% decrement in force at 2 min) compared with newborn DIA (28± 8% decrement in force at 2 min). Extracellular cytochromecreduction was greater in adult as compared with newborn DIA during fatiguing contractions. Exogenous SOD attenuated fatigue in the adult, but had no effect on newborn DIA. We conclude that the oxidative capacity of the adult DIA is greater than that of the newborn and not matched by a concomitant increase in SOD activity. Our data suggest that the increased oxidative capacity releative to SOD activity in adult DIA may lead to oxidative stress and an enhanced susceptibility to fatigue.Abbreviations: CAT,catalase;CSA,cross-sectional area;SOD,superoxide dismutase;Cu/Zn SOD,copper/zinc(cytosolic) SOD;Mn SOD,manganese (mitochondrial) SOD;DIA,costal diaphragm;GPX,glutathione peroxidase;GSH,glutathione;O2[horizontal line over dot], superoxide anion radical;ROS,reactive oxygen species;SDH,succinic dehydrogenase

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID