摘要:

Studies of the brains of severely birth-asphyxiated infants using proton(1H) magnetic resonance spectroscopy (MRS) have shown changes indicating a rise in cerebral lactate (Lac) and a fall inN-acetylaspartate (Naa). The aim of this study was to test two hypotheses:1) that these changes can be reproduced in the newborn piglet after transient reversed cerebral hypoxia-ischemia, and their time course determined; and2) that changes in Lac peak-area ratios are related to changes in phosphorylation potential as determined by phosphorus(31P) MRS. Eighteen piglets aged <24 h were anesthetized and ventilated. Twelve underwent temporary occlusion of the carotid arteries and hypoxemia, and six served as sham-operated controls.1H and31P spectra were acquired alternately, both during the insult and for the next 48 h, using a 7-tesla spectrometer. During hypoxia-ischemia, the median Lac/total creatine (Cr) peak-area ratio rose from a baseline of 0.14 (interquartile range 0.07-0.27), to a maximum of 4.34 (3.33-7.45). After resuscitation, Lac/Cr fell to 0.75 (0.45-1.64) by 2 h, and then increased again to 2.43(1.13-3.08) by 48 h. At all stages after resuscitation Lac/Cr remained significantly above baseline and control values. Naa/Cr was significantly reduced below baseline and control values by 48 h after resuscitation. The increases in the Lac peak-area ratios were concomitant with the falls in the[phosphocreatine (PCr)*]/[inorganic phosphate (Pi)] ratio, during both acute hypoxia-ischemia and delayed energy failure. The maximum Lac/Naa during delayed energy failure correlated strongly with the minimum[nucleotide triphosphate (NTP)]/[exchangeable phosphate pool (EPP)](r= -0.94,p< 0.0001). We conclude that both hypotheses have been confirmed.Abbreviations: Cho,choline-containing compounds;Cr,creatine plus phosphocreatine;EPP,exchangeable phosphate pool;FID,free induction decay;1H,proton;Lac,lactate;MABP,mean arterial blood pressure;MRS,magnetic resonance spectroscopy;Naa,N-acetylaspartate;NTP,nucleotide triphosphate;PCr,phosphocreatine;pHi, intracellular pH;Pi, inorganic phosphate;ppm,parts per million;PRESS,point-resolved spectroscopy;T2, transverse relaxation time;TR,repetition time

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This study tested the hypothesis that mild hypothermia after severe transient hypoxia-ischemia reduces the subsequent delayed rise in cerebral lactate peak-area ratios as determined by proton (1H) magnetic resonance spectroscopy (MRS) in the newborn piglet. Nine piglets aged <24 h underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine]/[inorganic phosphate] had fallen close to zero and [nucleotide triphosphate(NTP)]/[exchangeable phosphate pool (EPP)] was below about a third of baseline. On resuscitation rectal and tympanic temperatures were lowered to 35°C for 12 h after which normothermia (38.5 °C) was resumed.1H MRS data collected over 48 or 64 h after resuscitation were compared with concurrently established data from 12 piglets similarly subjected to transient cerebral hypoxia-ischemia, but maintained normothermic, and six shamoperated controls. The severity of the primary insult (judged from the time integral of depletion of [NTP]/[EPP]) was similar in the hypothermic and normothermic groups. The maximum lactate/N-acetylaspartate ratio observed between 24 and 48 h after resuscitation in the hypothermic group was 0.10 (0.05-0.97), median (interquartile range), which was significantly lower than that observed in the normothermic group, 1.28 (0.97-2.14), and not significantly different from that observed in the control group, 0.08 (0.06-0.11). Similar results were obtained for lactate/choline and lactate/total creatine. We conclude that mild hypothermia after a severe acute cerebral hypoxic-ischemic insult reduces the delayed elevation in lactate peak-area ratios, thus reflecting reduced lactate accumulation.Abbreviations: Cho,choline-containing compounds;Cr,creatine plus phosphocreatine;EPP,exchangeable phosphate pool;Fio2, inspired oxygen fraction;1H,proton;Lac,lactate;MABP,mean arterial blood pressure;MRS,magnetic resonance spectroscopy;Naa,N-acetylaspartate;PCr,phosphocreatine;Pi, inorganic phosphate;ANOVA,analysis of variance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We evaluated the effects of magnesium on extracellular dopamine (DA) and its metabolites in the striatum of 5-d-old rats submitted to 16 min of anoxia using microdialysis and HPLC. Rat pups were divided into three groups and received either1) intrastriatal perfusion (IS) of MgSO4,2) intraperitoneal injection (IP) of MgSO4, and3) NaCl and Ringer's solution, respectively in place of MgSO4. After stabilization, Mg2+, saline, and Ringer's solution were administered; then, 114 animals were exposed to 100% nitrogen for 16 min. Anoxia induced a DA surge, an acutely marked increase of DA, in both the control and the IP group. In contrast, the DA surge was significantly suppressed in the IS group(p< 0.01, analysis of variance). During anoxia, the plasma Mg2+in the IP group, but not in the IS group, maintained a significantly higher level compared with the basal level. On the other hand, Mg2+in the perfusates in the IS group, but not in the IP group, maintained a significantly high level during anoxia. Alterations induced by anoxia in other metabolites, 3,4-dihydroxyphenylacetic acid, homovanillic acid, norepinephrine, and 5-hydroxyindole-3-acetic acid, did not significantly differ among the three groups. We propose that elevated levels of Mg2+in the striatum had inhibitory effects on the DA surge during anoxia.Abbreviations: DA,dopamine;NE,norepinephrine;DOPAC,3,4-dihydroxyphenylacetic acid;HVA,homovanillic acid;5-HIAA,5-hydroxyindole-3-acetic acid;NMDA,N-methyl-D-aspartate;BBB,blood brain barrier;IP,intraperitoneal injection;IS,intrastriatal perfusion;HI,hypoxic ischemia(c);ANOVA,analysis of variance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Maternal cocaine abuse has been associated with fetal and neonatal neurologic abnormalities, including hemorrhagic cerebral infarctions, but the mechanisms for cocaine's cerebral effects are unknown. We previously showed that acute cocaine injection causes cerebral vasodilation in cats and immature sheep; others have shown that cocaine causes cerebral vasoconstriction in piglets and in pressurized neonatal sheep arteries. Although methodologic and species differences may explain these conflicting results, we tested another possibility; that is, that ecgonine methyl ester (EME), a major cocaine metabolite in sheep, causes cerebral vasodilation and may account, in part, for cocaine's vascular effects. We studied the cerebral effects of a single i.v. injection of EME (2.5 mg/kg) in eight chronically catheterized, unanesthetized neonatal sheep (4 ± 2 d old). We measured cerebral hemisphere blood flow (CBF) using radiolabeled microspheres, mean arterial pressure, heart rate, and arteriovenous oxygen content, and we calculated cerebral oxygen consumption (CMRo2) and cerebrovascular resistance at baseline and 0.5, 2, 5, and 60 min after EME injection. EME injection had no systemic effects, including no changes in mean arterial pressure, heart rate, or arterial blood gases. Within 0.5 min of injection, EME caused a 21% decrease in cerebrovascular resistance, which remained decreased for 60 min. CBF increased by 20% at 0.5, 2, and 5 min. Blood flow to brain regions other than the cerebral hemispheres paralleled changes in CBF, with cerebellar flow remaining increased at 60 min. There was no change in CMRo2. There was a small, but physiologically insignificant, decrease in arterial oxygen content. We conclude that EME causes cerebral vasodilation in neonatal sheep and may account, in part, for cocaine's cerebral vascular effects.Abbreviations: EME,ecgonine methyl ester;CVR,cerebral vascular resistance;CBF,cerebral blood flow;CMRo2, cerebral metabolic rate for oxygen;MAP,mean arterial pressure;Cao2, arterial oxygen content;Cvo2, venous oxygen content;BE,benzoylecgonine

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

There is reason to believe that dopamine is important in developmental programs of the basal ganglia, brain nuclei implicated in motor and cognitive processing. Dopamine exerts effects through dopamine receptors, which are predominantly of the D1and D2subtypes in the basal ganglia. Cocaine acts as a stimulant of dopamine receptors and may cause long-term abnormalities in children exposedin utero. Dopamine receptor(primarily D1) stimulation has been linked to gene regulation. Therefore, D1and D2receptor densities in perinatal and adult striatum and globus pallidus were examined using quantitative autoradiography. The most striking finding was that pallidal D1receptor densities were 7-15 times greater in the perinatal cases than in the adult. Pallidal D2receptor densities were similar at both ages. In both the adult and perinatal striatum, D2receptor densities were greater in the putamen than in the caudate, and both D1and D2receptor densities were modestly enriched in caudate striosomes compared with the matrix. In both caudate and putamen, perinatal D1receptor levels were within the adult range, whereas D2receptor levels were only 50% of adult values. The development of D1and D2receptors appears to vary across the major subdivisions of the human basal ganglia. The facts that we found such extremely high levels of D1receptors in the perinatal pallidum, and that D1receptor activation influences gene regulation, suggest that the globus pallidus could be particularly susceptible to long-term changes with perinatal exposure to cocaine and other D1receptor agonists or antagonists.Abbreviations: 5-HT2, serotonin-2 receptor;GABA,γ-aminobutyric acid;GPe,globus pallidus externa (lateralis);GPi,globus pallidus interna (medialis);HB,tissue homogenate receptor binding assay;IEG,immediate-early genes;SCH,SCH-23390 (a selective D1dopamine receptor antagonist);SPIP,spiroperidol (a selective D2dopamine receptor antagonist);QA,quantitative autoradiographic receptor assay

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Sympathetic innervation of cardiac myocytesin vitroinduces growth independent of anatomic contact between the neurons and myocytes and is not mediated by α- or β-adrenergic receptor stimulation. To establish a model system that will allow purification and identification of the neuronal factor(s) responsible for mediating this regulation, we have initiated studies utilizing conditioned medium from the PC12 cell line. PC12 cells acquire a cholinergic sympathetic neuronal phenotype when exposed to nerve growth factor. Culture medium conditioned by neuronal PC12 cells, but not nonneuronal PC12 cells, induces growth in newborn rat cardiac myocytes as measured by surface area and [35S]methionine incorporation into protein and increases expression of atrionatriuretic peptide, a marker for myocyte hypertrophy. The magnitude of the growth response is dose-dependent and mimics the response to sympathetic innervation. The myocyte response to conditioned medium is not detectable after 24 h of exposure; maximal rate of protein synthesis is obtained within 48 h. Neuronally differentiated PC12 cell-conditioned medium stimulation of growth could not be mimicked byα- or β-adrenergic agonists or muscarinic agonists, nor inhibited by α- or β-adrenergic antagonists, nor by muscarinic antagonists. Neuropeptide Y and somatostatin, peptides known to be present in PC12 cells and sympathetic neurons, were also ineffective at reproducing the effect of neuronally differentiated PC12 cell-conditioned medium. These data indicate that neuronal cells release a soluble factor, different from neurotransmitter, which stimulates myocyte growth. They further identify the PC12 cell line as providing a convenient and abundant supply of this molecule, thus facilitating its further characterization.Abbreviations: ANP,atrionatriuretic peptide;NGF,nerve growth factor;PCR,polymerase chain reaction;RT-PCR,reverse transcriptase polymerase chain reaction;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;nPC12,neuronally differentiated PC12 cells;cPC12,chromaffin PC12 cells;HEPES,N-2-hydropyethylpiperazine-N'-2-ethanesulfonic acid;MEM,minimal essential medium

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We previously observed young lambs to be more tolerant of hypoxia; compared with older lambs, they accumulate lactate at a slower rate during comparable reduction in cardiac output, and have a greater percent decrease in cardiac output before onset of systemic lactate accumulation. To determine the mechanism of lactic acidosis and the cause for this “tolerance,” we reduced cardiac output progressively in seven chronically catheterized conscious lambs (16.4 + 5.1 d) and measured hepatic and gastrointestinal (GI) blood flow (radioactive microspheres) and delivery, uptake, and extraction of lactate and O2. Hepatic O2consumption declined proportionately below a critical hepatic O2delivery (≅2 mL O2/min/kg), corresponding to the systemic O2delivery associated with the onset of systemic lactate accumulation. As hepatic O2delivery decreased below the critical value, there was initially net hepatic lactate uptake and then a change to net production when the O2delivery decreased below ≅1 mL O2/min kg. The GI tract had net lactate production at rest, but surprisingly switched to lactate uptake as cardiac output decreased. The mechanism of lactic acidosis was failure of hepatic lactate uptake to increase despite increased hepatic lactate delivery, as reported in adults subjects. However, in contrast, there was “true” hepatic dysfunction and lactate production only at the lowest levels of cardiac output, after onset of systemic lactate accumulation. Moreover, we speculate that tolerance of young lambs to hypoxia is at least due to two factors:1) hepatic lactate uptake is maintained beyond the “critical” O2delivery and fall in hepatic O2consumption, and2) there is a switch to lactate uptake by the GI tract serving to buffer the lactate.Abbreviations: GI,gastrointestinal;Hct,hematocrit;Hbo2, fractional Hb oxygen saturation

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

At between 7 and 11 h after delivery, 14 fasted calves were randomly divided into two groups to examine the effects of neonatal hypoxia on blood glucose metabolism and its mechanisms. One group was subjected to breathe a gas mixture containing 4.8-5.9% oxygen in nitrogen from a hood for 2 h. The second control group breathed atmospheric gas. Several possible causes of changes in blood glucose were assessed, including insulin, glucagon, and hydrocortisone as prereceptor factors, insulin binding as a receptor factor, and insulin receptor tyrosine kinase (IR-TK) activity as a postbinding factor. The hypoxic animals exhibited increased concentrations of blood glucose (from 5.47 ± 1.61 mmol/L to 7.97 ± 1.30 mmol/L), plasma insulin, and hydrocortisone, but decreased concentrations of glucagon. The percentage of specific binding activity decreased in the hypoxic group compared with the control group (12.71 ± 1.25%versus15.14 ± 1.27%,p< 0.01). Several parameters of insulin receptor binding,i.e.affinity constants, high and low binding capacities, and numbers of binding sites, showed a tendency to decrease after hypoxia. Only lower affinity binding sites decreased significantly. At the postreceptor level, IR-TK activity was decreased in the hypoxic group compared with controls. It is concluded that hypoxia induced insulin resistance in these newborn calves. The results suggest that the primary mechanism for insulin resistance in the hypoxic newborn was reduced insulin receptor responsiveness with attenuated activity of IR-TK at the postreceptor level.Abbreviations: IR-TK,insulin receptor tyrosine kinase;WGA,wheat germ agglutinin

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Maturation of the CNS in neonatal animals is dependent upon both sensory input and the constant availability of metabolic fuel. Previous reports indicate that the preferred metabolic substrate for the developing rat brain is lactate. In this study, we used the neonatal Sprague-Dawley rat to investigate a possible interactive role between touch and the regulation of serum lactate. Two hundred and fifty rats (postnatal d 0-7) were exposed to a standard tactile stimulation (TS) regimen to mimic nonspecific maternal stimulation. This regimen consisted of stroking the dorsum with a soft camel hair brush for 30 s every minute for 10 min. Serum lactate and glucose levels were measured after TS. In newborn (d 0) rats, lactate levels were increased by 207% in stroked pupsversuscontrols. This elevation of serum lactate persisted for 30 min after cessation of TS. On d 7, TS increased lactate only 11%. Glucose levels were unaffected at all ages. In neonatal pups, pretreatment with pentobarbital blocked the effect of TS, whereas epidermal growth factor evoked a synergistic response. Capsaicin pretreatment had no effect. Mixed arteriovenous blood gases revealed a mild increase in pH and a decrease in Pco2after TS. We conclude that TS in newborn rats is a regulator of circulating lactate. This response is maximal in the immediate postnatal period and wanes over the 1st wk of life. We speculate that the transduction of sensory signals by the skin is a mechanism regulating the availability of cerebral energy substrates in the newborn mammal.Abbreviations: EGF,epidermal growth factor;ODC,ornithine decarboxylase;TS,tactile stimulation

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID