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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 397 records · Page 22Linked to original sources
PubMed1981

Neurochemical characteristics of cerebral catecholamine neurons during the postnatal development in the rat.

The development of cerebral dopamine (DA) and noradrenaline (NA) neurons was studied biochemically in 1- to 28-day-old rats. The precursor amino acid tyrosine increased to a steady state level in the whole brain during early postnatal age. After 14 days, however, there was a marked drop in the brain tyrosine level. In general, regional tyrosine levels also decreased between 4 and 28 days. DOPA accumulation was measured in whole brain and regional brain areas after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. This is a well recognized method for estimating the in vivo rate of tyrosine hydroxylase activity. Whole brain DOPA accumulation after NSD 1015 increased progressively during postnatal life, and between 1 and 28 days a more than 3-fold increase was noted. Similar increases were also found in whole brain DA and NA levels during the corresponding period. Regional DA and NA levels generally increased with advancing age, with the highest DA levels in the striatum region and NA levels in the midbrain region. Regional DOPA accumulation after NSD 1015, reflecting in vivo tyrosine hydroxylase activity, increased in a similar fashion as the endogenous neurotransmitter levels. Measurements of DA and NA disappearance after alpha-methyltyrosine indicated the existence of an adult-like nerve impulse activity in DA neurons in the striatum and midbrain regions and in NA neurons in the hemispheres region of the 4-day-old rats. Gammahydroxybutyric acid (GHBA), which causes an inhibition of nerve impulse activity, was given to 4- and 28-day-old rats. This induced an initial increase in CA synthesis as measured by the NSD 1015 method at both ages. The results from this investigation show that the age-related regional increases in endogenous DA and NA levels closely follow the increase in regional tyrosine hydroxylase activity measured in vivo. Furthermore, the study also supports the view that feed-back mechanisms, resulting in an increased transmitter synthesis, exist in DA neurons after nerve impulse inhibition by GHBA at an early postnatal age.

Age Factors↗
PubMed1980

Serotoninergic development in the postnatal rat brain.

Various characteristics of the developing serotoninergic system in the brain of rats aged 1 to 28 days were studied biochemically. The levels of the precursor amino acid tryptophan showed a maximal increase in the blood, brain and cerebrospinal fluid (CSF) during the 7th and 10th postnatal days. The development of tryptophan hydroxlyase activity measured in vivo by means of 5-hydroxytryptophan (5-HTP) accumulation after NSD 1015 was closely related to the 5-hydroxytryptamine (5-HT) levels at the various ages. 5-HTP accumulation and 5-HT levels increased most markedly after the second postnatal week. 5-Hydroxyindoleacetic acid (5-HIAA) levels were found to increase rapidly in the brain but somewhat more slowly in the CSF during the second week of postnatal development. Regional studies of 5-HTP accumulation after NSD 1015, 5-HT and 5-HIAA levels indicated a caudal to rostral way of maturation. The disappearance of 5-HT was measured after inhibition of tryptophan hydroxylase with H 22/54. The half-life generally decreased in the various brain parts with advancing age, and in the younger animals the shortest half-life was found in the most caudal brain parts. At 28 days of age the half-life was similar in all brain parts studied. These results indicate the existence of an adult like nerve impulse flow in the 5-HT neurons in the brain stem region of the newborn rats. The results from this investigation clearly indicate that th maturation of the different biochemical parameters of the 5-HT pathways develop in a caudal to rostral direction. The study also supports the view that tryptophan hydroxylase may be the limiting step in the development of the serotoninergic system.

5-Hydroxytryptophan↗
PubMed1980

Catecholamine concentration in the developing rat brain after gamma-hydroxybutyric acid.

The effect of the GABA receptor agonist gamma-hydroxybutyric acid (GHBA) on brain catecholamine concentration was investigated in 1 to 28 day old rats. The infant rats were given GHBA in various doses (375--1500 mg/kg) and the effects on whole brain or regional brain concentration of dopamine (DA) and noradrenaline (NA) were measured. Brain DA concentration increased in a dose-dependent way already from two days of postnatal age. In the regional brain study of the 14- and 28-day-old animals the increase in DA concentration was found to be almost exclusively located in the striatal region. Generally, no changes in NA concentration were found in the whole brain or various brain regions at any of the ages after GHBA. It is concluded that the inhibitory striatal-nigral neurons, utilizing GABA as a transmitter, are functionally developed during early postnatal age.

Aging↗
PubMed1980

Serotonin metabolism in neonatal rat brain during asphyxia and recovery.

Neonatal rats were exposed to 20 or 30 min of total or partial oxygen deprivation. During asphyxia and subsequent recovery the endogenous levels of tryptophan and 5-hydroxytryptamine (5-HT, serotonin) were measured. The activity of tryptophan hydroxylase, the first and rate limiting enzyme in the 5-HT synthesis pathway, was studied in vivo by measuring the accumulation of 5-hydroxytryptophan (5-HTP) after inhibition of aromatic L-amino acid decarboxylase with NSD 1015. During asphyxia there was a decrease in tryptophan hydroxylase activity in the whole brain and various regions studied. The levels of tryptophan, 5-HTP and 5-HT all increased after 30 min of recovery from asphyxia. In the whole brain, 5-HTP and 5-HT levels were normal 2 h after anoxia while tryptophan levels normalized more slowly to reach control values after 6 h. In the regional brain study, the 5-HTP levels returned quickly to control levels after asphyxia in the striatum and midbrain but not in the brainstem and hemispheres regions. The whole brain 5-HTP and 5-HT levels did not differ from controls 24 to 48 h after the asphyxia. Although the neonatal nervous system exhibits a great resistance to asphyxia, the metabolism of the neurotransmitter 5-HT is affected already during a short period of asphyxia and subsequent recovery. As 5-HT is ascribed important neurotransmitter functions, this might be relevant to the neurological sequelae of human asphyxia neonatorum.

5-Hydroxytryptophan↗
PubMed1980

Pressure-volume relationship and fluid content in fetal rabbit lung after beta-receptor-stimulating drugs.

A considerable interest has been focused on the effects of various drugs on fetal and neonatal pulmonary maturation and adaptation. In the present study, we have investigated the effects of the selective beta1- and beta2-receptor-stimulating agents prenalterol and terbutalilne on the pressure-volume relationship and fluid content in fetal rabbit lung at 28 days of gestation. Pressure-volume recordings during deflation showed significantly increased lung volumes at equivalent transpulmonary pressures in terbutaline-treated fetuses as compared to controls. No such effect was noted after prenalterol. In the control animals, wet lung weight/body weight ratio decreased to a steady state level 60 min after birth, indicating a rapid dehydration of the lungs. This dehydration was present at delivery after terbutaline and prenalterol treatment. The amount of fluid collected from the airways was also reduced after terbutaline and prenalterol treatment. The present results indicate facilitated neonatal respiratory adaptation after especially terbutaline treatment. Possible mechanisms behind these effects are discussed.

Adrenergic beta-Agonists↗
PubMed1980

Respiratory depression by GABA-ergic drugs in the preterm rabbit.

Respiratory parameters were studied in preterm rabbits (gestational age 29 days) after intraperitoneal administration of the GABA-like drugs gamma-hydroxybutyric acid and muscimol. The animals were anaesthetized with 0.7% halothane in oxygen and studied in a closed body plethysmograph. Both drugs induced a decreased respiratory frequency and minute volume. Tidal volume decreased after muscimol, but not after gamma-hydroxybutyric acid administration. The present results indicate that an increased GABA-ergic activity causes respiratory depression in the preterm neonatal rabbit, presumably by an action on central nervous frequency and tidal volume modulating systems. Central GABA neurons may thus be involved in the pathogenesis of neonatal respiratory depression and irregular breathing.

Animals↗
PubMed1980

Adrenal catecholamines during and following hypoxia in neonatal rats.

The synthesis and content of adrenal catecholamines during hypoxia (6% O2) and the following recovery period were investigated in 4-day old rats. Adrenal catecholamine synthesis, as indicated by the dopamine content of the glands, increased significantly during hypoxia. During hypoxia a significant decrease in the adrenal noradrenaline but not adrenaline content was noted. In the recovery period following 30 min of hypoxia the noradrenaline level was rapidly restored to the control value. The results show that hypoxia causes increased catecholamine synthesis in the immature rat adrenal gland, presumably mediated by an increased tyrosine hydroxylase activity induced via the splanchnic nerves. In the neonate rat hypoxia seems to stimulate the release of a larger proportion of noradrenaline than adrenaline from the adrenal glands when compared to the adult animal.

Adrenal Glands↗
PubMed1979

Regional changes in monoamine synthesis in the developing rat brain during hypoxia.

4, 14 and 28 days old rats were exposed to hypoxic environment of 6% O2-94% N2 for 30 min. Tyrosine hydroxylase and tryptophan hydroxylase activity was studied in different brain regions (hemispheres, striatum, midbrain and brainstem in vivo by measuring the accumulation of dihydroxyphenylalanine (Dopa) and 5-hydroxytryptophan (5-HTP) respectively, after inhibition of aromatic L-amino acid decarobyxlase with NSD 1015. Tyrosine and tryptophan levels in the different brain regions were measured simultaneously. The tyrosine and tryptophan levels in the various brain parts were generally not influenced during exposure to hypoxia. Tyrosine hydroxylase activity decreased in most areas in the 4 and 14 days old rats, and all brain areas studied in the 28 days old rats. Tryptophan hydroxylase activity decreased markedly in all brain areas at all ages studied. It is concluded that the enzymes tyrosine hydroxylase as well as tryptophan hydroxylase seem to be equally affected during hypoxia in the different brain regions studied.

5-Hydroxytryptophan↗
PubMed1978

Effect of hypoxia on monoamine synthesis in brains of developing rats. III. Various O2 levels.

1-, 4-, 14- and 28-day-old rats were exposed to a hypoxic environment of 5.9, 8.0 or 12.0% O2 during a period of 30 min. In the brain, tyrosine hydroxylase and tryptophan hydroxylase activity was studied in vivo by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. Tyrosine and tryptophan levels in the brain were measured simultaneously. The brain tyrosine and tryptophan levels were generally not influenced either by age or hypoxic levels. Tyrosine and tryptophan hydroxylase activity decreased to about the same extent during the various hypoxic levels at all ages studied. It is concluded that the first, rate-limiting, step in the synthesis of the monoamine neurotransmittors dopamine (DA), noradrenaline (NA) and 5-hydroxy-tryptophan (5-HT) is affected during moderate as well as severe hypoxia at all stages of development.

5-Hydroxytryptophan↗
PubMed1978

Effects of terbutaline on the pressure volume relationship in fetal rabbit lung.

The pressure-volume relationship in preterm rabbit lung was studied at 28 days of gestation. Injection of 0.1 mg terbutaline, a selective beta2-receptor stimulating drug, significantly increased the volume of air at equivalent low transpulmonary pressures, compared to a saline treated group and an untreated group. These findings indicate an increased pulmonary distensibility of the fetal rabbit lung after terbutaline administration. The mechanism of action is discussed and surfactant mediated effects are suggested to be the probable explanation.

Animals↗
PubMed1978

Antepartum administration of terbutaline and the incidence of hyaline membrane disease in preterm infants.

The incidence of hyaline membrane disease in 41 preterm infants born between January 1975 and January 1976 was investigated in a retrospective study. Terbutaline, a beta2-receptor stimulating drug, had been administered to the women in order to arrest premature labour. In spite of the treatment 24 preterm infants were delivered. The incidence of HMD in this group was 1/24. In a group of 17 neonates whose mothers had received no such treatment the incidence of HMD was 5/17. Comparison between the two groups revealed a significantly lower incidence of HMD in the terbutaline treated group than in the controls (p less than 0.05). There were no significant differences in maternal age, gestational age, birth weight or Apgar score between the two groups. The lower incidence of HMD in the terbutaline treated group is suggested to reflect a rapidly induced release of pulmonary surfactants in the preterm infants. Evidence for a similar sequence of events has earlier been shown to occur in animals under standardized experimental conditions.

Administration, Oral↗
PubMed1977

Effect of hypoxia on monoamine synthesis in brains of developing rats.

Tyrosine and tryptophan hydroxylase activity was studied in the postnatal rat brain in vivo by measuring the accumulation of dihydroxyphenylalanine and 5-hydroxytryptophan, respectively after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. With increasing age there was a significant increase in the amount of dopa and 5-HTP accumulated in the brain after administration of NSD 1015. After 30 min in a 12% oxygen environment there were significant reductions of tyrosine hydroxylase and tryptophan hydroxylase activity at 1,14 and 28 but not 4 days of postnatal age. Further, the decrease in 5-HTP accumulation was significantly more marked at 14 and 28 days than at 1 day of age. Thus, the oxygen-dependent synthesis of the neurotransmitter 5-hydroxytryptamine seems to be less vulnerable in the early postnatal rat brain.

5-Hydroxytryptophan↗