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Biomedical subjects

H Lagercrantz

Publications and source records attributed to H Lagercrantz.

At least 19 recordsLinked to original sources
PubMed1995

Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome.

The drive on respiration mediated by the peripheral arterial chemoreceptors was assessed by the hyperoxic test in 3-day-old rat pups. They accounted for 22.5 +/- 8.8% during control conditions, but only for 6.9 +/- 10.0% after nicotine exposure, an effect counteracted by blockade of peripheral dopamine type 2 receptors (DA2Rs). Furthermore, nicotine reduced dopamine (DA) content and increased the expression of tyrosine hydroxylase (TH) in the carotid bodies, further suggesting that DA mediates the acute effect of nicotine on arterial chemoreceptor function. During postnatal development TH and DA2R mRNA levels in the carotid bodies decreased. Thus, nicotine from smoking may also interfere with the postnatal resetting of the oxygen sensitivity of the peripheral arterial chemoreceptors by increasing carotid body TH mRNA, as well as DA release in this period. Collectively these effects of nicotine on the peripheral arterial chemoreceptors may increase the vulnerability to hypoxic episodes and attenuate the protective chemoreflex response. These mechanisms may underlie the well-known relation between maternal smoking and sudden infant death syndrome.

Animals↗
PubMed1995

Improved understanding of respiratory control--implications for the treatment of apnoea.

Recurrent apnoea of prematurity should probably be regarded as more or less a physiological phenomenon providing that it is not precipitated by for example septicaemia and cerebral haemorrhage since the fetus of the corresponding age is only breathing episodically. Neonatal apnoea is probably not caused by a deficient respiratory rhythmic regeneration, but rather by respiratory inhibitory mechanisms induced by hyperthermia, hypoxia and adenosine. A more physiological approach should be taken in the treatment of apnoea. Some warning against the extensive use of xanthine derivatives should be raised.

Apnea↗
PubMed1995

Monoamine neurotransmitters and metabolites in the cerebrospinal fluid following perinatal asphyxia.

While the release of neurotransmitters is involved in the pathophysiology of brain damage following birth asphyxia, it also plays a role in endogenous defense against such damage. Levels of monoamines and the main cerebral monoamine metabolites in the cerebrospinal fluid (CSF) were measured in asphyxiated and control infants within 24 h after birth. The results indicate an increased turnover of noradrenaline (NA) and dopamine following asphyxia. Furthermore, the NA stores in the brain seem to be exhausted in some cases. We conclude that this increase in catecholamine turnover to some extent explains the clinical symptoms of hypoxic-ischemic encephalopathy and that it may reflect an intrinsic adaptive capacity to perinatal distress.

Asphyxia Neonatorum↗
PubMed1995

Birth-related up-regulation of mRNA encoding tyrosine hydroxylase, dopamine beta-hydroxylase, neuropeptide tyrosine, and prepro-enkephalin in rat adrenal medulla is dependent on postnatal oxygenation.

The transynaptic splanchnic regulation of the adrenal medulla is not functional in the newborn rat. Thus, synthesis and release of adrenal catecholamines and peptides are assumed to be regulated by nonneuronal mechanisms at this stage. In a previous study we reported 4-5-fold increases in the levels of mRNA encoding tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and neuropeptide tyrosine (NPY) in the rat adrenal medulla immediately after birth. In the present in situ hybridization study the importance of postnatal oxygenation for the birth-related increase in expression of these mRNA, and of preproenkephalin (ENK) mRNA was investigated in rat pups. We report here that maternal hypoxia (11-13% O2) leads to 2-3-fold increases (p < 0.01) in fetal adrenal TH, DBH, and NPY mRNA levels on the day before birth. These mRNA then further increased 1-5-2-fold (p < 0.01) 12 h after birth in room air. Only ENK mRNA levels increased (5-fold; p < 0.01) when pups were born in 11-13% O2; however, still less (p < 0.01) than after birth in room air when it increased nine times (p < 0.01). Thus, the birth-related increases in TH, DBH, NPY, and ENK mRNA levels in the rat adrenal medulla are dependent on postnatal oxygenation.

Adrenal Medulla↗
PubMed1995

Expression of c-fos, tyrosine hydroxylase, and neuropeptide mRNA in the rat brain around birth: effects of hypoxia and hypothermia.

Arousal at birth is likely to be accompanied by changes in gene expression patterns in the brain. We analyzed the expression levels of genes that may be involved in neonatal adaptation. We have also tried to dissect the effect of hypoxia and hypothermia, two components that may play a role in gene expression at birth. Therefore, we analyzed the expression patterns of the c-fos, tyrosine hydroxylase, enkephalin, preprotachykinin-A, and neuropeptide Y genes in various brain regions of rat pups at various time points after cesarean section under normal conditions and after exposure to hypoxia and hypothermia. We found that c-fos RNA was up-regulated transiently after birth in neocortex, midbrain, and pons-medulla with a maximum of 30 min after cesarean section, and that this transient increase was not further augmented by hypoxia and hypothermia. The expression patterns of the other genes were not significantly altered, with the exception of a very slight increase in tyrosine hydroxylase RNA levels. We discuss tentative mechanisms for the transient increase in c-fos expression and the possible involvement of catecholamines in this process.

Animals↗
PubMed1994

Neuronal markers, peptides and enzymes in nerves and chromaffin cells in the rat adrenal medulla during postnatal development.

Neuronal markers, peptides and enzymes were analyzed in the rat adrenal medulla during the postnatal period, i.e., when the 'functional' splanchnic innervation is assumed to 'mature'. Nerve fibers were present on day 2 as indicated by neurofilament 10 (NF10)- and growth associated protein 43 (GAP43)-like immunoreactivities (LIs). Acetylcholinesterase (AChE)- and enkephalin (ENK)-immunoreactive (IR) fibers, presumably of preganglionic nature, increased in number and intensity during the postnatal period. In contrast, calcitonin gene-related peptide (CGRP)- and galanin (GAL)-IR fibers were almost fully developed on day 2. Thus, the presumably sensory innervation of the adrenal gland seems to precede the development of the autonomic nerves. The AChE- and ENK-IR fibers may exert a suppressive effect on ENK-, CGRP- and neurotensin (NT)-LIs in chromaffin cells, since the levels of these peptides were high in the early postnatal period and then decreased. On the other hand, GAL-LI in chromaffin cells was low also in young rats, while GAP43-IR cells were observed at all stages. Neuropeptide tyrosine (NPY) was expressed in many chromaffin cells at all stages and its turnover rate seemed to decrease towards the adult stage. The expression of the catecholamine synthezising enzymes changed only marginally during development. These results indicate that the preganglionic fibers, but not the sensory axons, in the splanchnic nerve are involved in the developmental control of expression of some, but not all, peptides in the chromaffin cells and that these changes thus may reflect the maturation of a 'functional' transmission.

Acetylcholinesterase↗
PubMed1994

Effects of NMDA and non-NMDA receptor antagonists on inspiratory neurons in the in vitro brainstem-spinal cord preparation of newborn rat.

We examined the effects of N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (APV) and non-NMDA antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on inspiratory neurons in the medulla oblongata and C4 and C5 ventral root activity in the in vitro brainstem-spinal cord preparation of newborn rats. Application of APV induced increased rate of inspiratory neuron bursts, and decreased burst duration. The C4 burst activity was almost abolished by application of CNQX, whereas inspiratory neurons continued to discharge rhythmically. The results suggest that non-NMDA receptors are not crucially involved in the medullary respiratory rhythmogenesis, and that NMDA-mediated neurotransmission could modify the respiratory pattern, in the in vitro model.

2-Amino-5-phosphonovalerate↗
PubMed1994

Hypoxic ventilatory defence in very preterm infants: attenuation after long term oxygen treatment.

The activity of peripheral chemoreceptors was studied in 19 preterm very low birthweight infants at the postconceptional age of 36 and 40 weeks using the hyperoxic test. The infants were in a healthy condition and did not receive any extra oxygen or medication when tested. The inhalation of pure oxygen caused a decrease in mean (SE) ventilation by 16.1 (2.6)% and 15.1 (2.1)% at the 36th and 40th gestational week respectively. At the 36th gestational week the ventilatory response was significantly slower than at 40 weeks (10.9 (6) and 7.3 (3) sec). Six infants who had been on supplemental oxygen for more than 21 days (from 21 to 56 days) responded with significantly lower response to hyperoxia at the 36th gestational week (-7.9 (3.6)%) than those receiving oxygen treatment for a shorter period of time, 0 to 16 days (-19.9 (3.2)%). The 'low responding' group included three infants who had suffered from chronic lung disease. Those infants showed the lowest hyperoxic response (-4.3 (3.9)%). There was no difference in the response among healthy preterm infants (eight infants) and infants with respiratory distress syndrome. At the 40th gestational week the differences, even though showing the same characteristics, were not statistically significant. No statistically significant relationship was found between the strength of the ventilatory response to oxygen versus gestational, postnatal age, nor the time interval between the termination of supplemental oxygen treatment and the test. No relationship was found between the number of apnoeic/bradycardic spells and the strength of the ventilatory depression caused by hyperoxia. In conclusion we found that the very preterm infants, with the exception of those who received long periods of oxygen treatment, have stronger peripheral chemoreceptor responses than those reported for 2-4 day old full term infants. However, infants who had suffered from chronic lung disease show a depressed hyperoxic response.

Chemoreceptor Cells↗
PubMed1994

Birth-related changes of expression and turnover of some neuroactive agents and respiratory control.

Respiratory movements are partially inhibited before birth and central and peripheral chemoreceptors are probably less sensitive. The transition to continuous breathing might be due to the switch-off of inhibitory neuromodulators and the switch-on of excitatory neuroactive agents. This hypothesis has been explored mainly in rats. One example is dopamine which was found to have a high turnover in carotid bodies in newborn pups prior to decreasing rapidly. It is suggested to inhibit the carotid bodies before birth. In the brain, the noradrenergic system has been found to be activated at birth, possibly promoting neural transmission and arousal. Increased expressions of mRNA for c-fos, tyrosine hydroxylase and some neuropeptides have also been found.

Animals↗
PubMed1993

Expression of members of the trk family in the developing postnatal rat brain.

Tyrosine protein kinases trk, trkB and trkC are essential components of the high affinity receptors necessary to mediate biological effects of the neurotrophins NGF, BDNF, NT-3 and NT-4. Here we report on the expression of these receptors during postnatal development in the rat brain. Cells expressing mRNAs encoding different members of the trk family were identified by in situ hybridization using oligonucleotides complementary to their respective mRNA. In septum, striatum and brainstem, higher levels of trk mRNA were detected at 2 and 4 weeks than at 1 weeks of age. In thalamic nuclei associated with the limbic system, trkB and trkC mRNA were highly expressed at P1 to P7, but the expression declined gradually in 2 and 4 week old animals. Other structures where a developmentally regulated expression was seen included the tenia tecta and piriform cortex where trkB mRNA was not detected until 2 weeks of age. A high labeling was found for trkC mRNA in the deeper parts of neocortex in P1 and P4 animals, while in 2 and 4 weeks old animals the highest labeling was seen over the outer neocortical layers. Several brainstem nuclei showed a higher labeling for trkC mRNA at P1 to P7 than in animals of older age. These data show that expression of members of the trk family is developmentally regulated during postnatal brain development and suggest that high affinity neurotrophin receptors mediate a transient response to neurotrophins in many regions during brain ontogeny.

Aging↗
PubMed1993

Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic-ischemic encephalopathy.

Asphyxiated (n = 27) and control infants (n = 25) were subjected to spinal taps. Amino acids were measured with liquid chromatography and the degree of hypoxic-ischemic encephalopathy was determined in each case. In asphyxiated infants, the concentrations of aspartate and glutamate were 286% and 387% (p < or = 0.01 and p < or = 0.05) of the control values, respectively. The cerebrospinal fluid aspartate levels were significantly (p < or = 0.05) higher in the group with severe (3.4 mumol/l) compared with the group with mild hypoxic-ischemic encephalopathy (1.0 mumol/l). Glutamate was also higher in the group with severe (12.3 mumol/l) than in the groups with mild (2.7 mumol/l) or moderate (3.2 mumol/l) hypoxic-ischemic encephalopathy (p < or = 0.05). High concentrations of excitatory amino acids were present in the CSF of asphyxiated infants which may exert excitotoxic effects.

Amino Acids↗