Role of histamine in spinal cord evoked potentials and edema following spinal cord injury: experimental observations in the rat.
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Animals↗
Biomedical subjects
F Nyberg
Publications and source records attributed to F Nyberg.
Vascular permeability to growth hormone in the rat central nervous system after focal spinal cord injury. Influence of a new anti-oxidant H 290/51 and age.
Vascular permeability to the growth hormone (GH) across the blood-brain barrier (BBB) is unknown. This investigation was undertaken to examine vascular permeability to 125I-labelled rat growth hormone (rGH) in the central nervous system (CNS) of normal animals. Since age and spinal cord injury influences the metabolism of GH, these factors were also included. No statistically significant difference was seen regarding rGH permeability between young (aged 19-21 weeks) and old (age 38-42 weeks) animals. A focal trauma to the cord, produced by an incision into the right dorsal horn of the T10-11 segments in young animals, increased rGH permeability in several spinal cord segments at 0.5-5.0 h after injury. This permeability increase progressed over time. Similar trauma to old rats resulted in a significantly less increase in rGH permeability in the spinal cord 5 h after the trauma. This indicates that trauma-induced increased permeability of rGH is age-dependent. Pretreatment of normal young animals with a new antioxidant (H 290/51) did not influence the rGH permeability. However the drug prevented the trauma-induced increase of rGH permeability at 5 h after injury. This indicates that inhibition of lipid peroxidation has some protective effect on trauma-induced increase in rGH permeability.
Aging↗
Morphine-induced prolactin release precedes a down-regulation of prolactin receptors in the male rat choroid plexus and hypothalamus.
In previous studies we provided evidence for changes in prolactin (PRL) receptor levels in the male rat brain after continuously infusing morphine using subcutaneously implanted miniosmotic pumps. In this work we have studied the binding of PRL in the male rat brain following morphine administration by both subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injections. The binding in the choroid plexus and the hypothalamus was measured using iodinated ovine PRL (oPRL) as a radiolabel. The results indicated that the density of the PRL-binding sites in the hypothalamus and the choroid plexus were significantly decreased 4 h and 24 h after s.c. injections, and also 30 min and 4 h after i.c.v. injections. However, no decrease in PRL-binding was observed 15 min after i.c.v. injection of morphine. The plasma levels of PRL were measured by radioimmunoassay (RIA) and were found to be significantly increased after 30 min and 4 h in all treated animals. Following i.c.v. injection a significant increase in plasma PRL was observed after just 15 min. It was suggested that the down-regulation in PRL binding to some extent at least resulted from receptor overstimulation caused by the morphine-induced elevation in the concentrations of the endogenous hormone.
Animals↗
Neuropeptide converting and processing enzymes in the spinal cord and cerebrospinal fluid.
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Amino Acid Sequence↗
The opioid receptor antagonist naloxone influences the pathophysiology of spinal cord injury.
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Animals↗
Influence of dynorphin A antibodies on the formation of edema and cell changes in spinal cord trauma.
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Animals↗
Calcitonin gene related peptide gene expression in collagen-induced arthritis.
Changes in calcitonin gene related peptide (CGRP) gene expression in spinal motoneurons and dorsal root ganglia (DRG) of rats subjected to collagen II induced arthritis (CIA) were evaluated by semiquantitative in situ hybridization. The effects of systemic treatment with the corticosteroid budesonide on basal CGRP expression and on changes under inflammatory conditions were examined. CIA caused a significant increase in CGRP mRNA levels in DRG. Budesonide reduced the constitutive CGRP mRNA levels in DRG, compared with untreated control rats, and reversed the CIA-induced increase. In contrast, CIA caused a marked decrease of CGRP mRNA levels in motoneurons. Budesonide had no effect on constitutive CGRP mRNA levels in motoneurons and attenuated the decrease in CGRP mRNA levels in motoneurons of rats subjected to CIA. Thus, peripheral inflammation and systemic corticosteroids have differential effects on CGRP expression in sensory and motor neurons. This may be relevant for the pathophysiology and pharmacotherapy of chronic inflammatory pain and motor dysfunction in chronic arthritis.
Animals↗
Reversed-phase high-performance liquid chromatography for the determination of haemorphin-like immunoreactivity in human cerebrospinal fluid.
The haemorphins are opioid peptides derived form the blood protein haemoglobin. This study was focused on the detection and determination of haemorphin-like immunoreactivity in human cerebrospinal fluid (CSF) by reversed-phase HPLC. For this purpose a SMART System, optimized for micropurification, was applied. Prior to application to HPLC, the peptide fraction of the CSF sample was extracted using a reversed-phase silica gel cartridge (Sep-Pak C18). In the HPLC separation, the peptide-like material associated with haemorphin-7 immunoreactivity was recovered and determined using a UV detector. The tryptophan residue present in the haemorphin sequence allowed UV detection at wavelengths (e.g., 276 nm) where interference with other co-eluting peptides lacking this residue is minimized. Recorded levels of haemorphin-like immunoreactivity were compared with those detected by radioimmunoassay.
Amino Acid Sequence↗
Effects of morphine on prolactin receptors in the rat brain.
The effect of chronically given morphine on the binding of ovine prolactin (oPRL) to specific areas in the male rat brain was studied. The drug was delivered through subcutaneously implanted miniosmotic pumps. The results indicated that the density of prolactin binding sites in the hypothalamus and the choroid plexus was significantly decreased in the acute phase of morphine administration but restored to control levels when tolerance to morphine was developed. The decrease in prolactin binding was contrasted by elevated plasma levels of the hormone. A negative correlation was found between the hormone concentration in plasma and the density of its binding sites in the hypothalamus and choroid plexus. The hormone-binding sites in these two regions were further characterized with regard to binding constants and molecular sizes. The relevance of the present results with respect to the hypothalamic control of prolactin secretion is discussed.
Animals↗
Characterization of neurotensin-like immunoreactivity in human cerebrospinal fluid by high-performance liquid chromatography combined with mass spectrometry.
This report describes the recovery and characterization of neurotensin-like immunoreactivity (NT-LI) in human cerebrospinal fluid (hCSF). A large quantity of the fluid was fractionated by gel filtration, and subsequently separated and analysed by different high-performance liquid chromatography (HPLC) systems. The recovered material was analysed by microLC continuous-flow fast atom bombardment mass spectrometry, where a close similarity between one active CSF component and native neurotensin was confirmed. It was also found that, although a certain amount of the total NT-LI behaved as authentic neurotensin, the major part of the immunoreactive material was likely to be due to prestages and metabolites of the active peptide. The present finding is of importance for the development of efficient procedures for the quantitative analysis of neurotensin in hCSF samples.
Amino Acid Sequence↗
Naloxone reduces alterations in evoked potentials and edema in trauma to the rat spinal cord.
The influence of naloxone (an opioid receptor antagonist) on spinal cord conduction and edema formation as a result of trauma to the cord was investigated in a rat model. The spinal cord injury (SCI) was inflicted in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of the T10-11 segments, about 2 mm deep and 5 mm long. Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. The edema was measured by determining water content of the cord at s h after injury. In rats not given naloxone SCI resulted in an immediate long-lasting depression of the rostral maximal negative peak (MNP) amplitude (about 60%) and a significant increase in the latency of the rostral maximal positive peak (MPP). Pretreatment with naloxone inhibited the immediate post-injury decrease of the rostral MNP and some of the increase of MPP latency. The water content in the traumatized spinal cord was reduced by 3% in naloxone treated animals compared with untreated injured controls. Our results indicate that endogenous opioid peptides participate in changes of spinal cord conduction after trauma and influence edema formation probably via multiple opioid receptors.
Afferent Pathways↗
Role of serotonin and prostaglandins in brain edema induced by heat stress. An experimental study in the young rat.
The possibility that serotonin and prostaglandins participate in edema formation following heat stress (HS) was examined in young rats. Exposure of conscious young animals (8-9 weeks old) to heat at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%; wind velocity 20-25 cm/s) for 4 h resulted in marked increase in the whole brain water content (about 3%) as compared to animals kept at room temperature (21 degrees C). A marked extravasation of Evans blue and 131I-sodium occurred in the brain of heat exposed animals as compared to normal animals. Morphological examination using electron microscopy of selected brain regions of heat stressed animals showed profound cell changes. Thus perivascular edema, swollen neuronal and glial cells, membrane damage, vesiculation of myelin, axonal swelling and synaptic damage was frequent in this group of untreated animals. Pretreatment with ketanserin (a selective serotonin2 receptor antagonist) or indomethacin (an inhibitor of prostaglandin synthesis) markedly reduced edema formation after 4 h HS in young animals. These heat stressed animals had considerably less extravasation of protein tracers as compared to the untreated group. Cell changes and edema at the ultrastructural level were mainly absent. Our results suggest that serotonin and prostaglandins are involved in heat stress induced breakdown of the BBB permeability, edema formation, and cell damage.
Animals↗
Cholecystokinin receptor binding in morphine analgesia: tolerance, withdrawal and abstinence.
The effect of morphine treatment on cholecystokinin (CCK) receptor binding in rat cerebral cortex was investigated. Subcutaneous implantation and removal of Alzet miniosmotic pumps, releasing morphine, permitted us to establish the phases of initial analgesia, tolerance to the analgesic action of morphine, morphine withdrawal and abstinence. CCK receptor binding in rat cerebral cortex never differed from the values obtained from animals implanted with saline-releasing minipumps. The results of the present study suggest that the putative changes in the interaction between opioidergic and CCKergic neurotransmission at different stages of morphine treatment and withdrawal are not caused by changes of CCK receptor binding properties.
Analgesia↗
Sex differences in binding of human growth hormone to rat brain.
The binding of 125I-human growth hormone (125I-hGH) to membranes from female and male rat brain was studied. The binding was time-, pH- and protein concentration-dependent. The binding capacities calculated for the hormone were higher in the female brain (12.1 fmol/mg protein) than in the male brain (4.5 fmol/mg protein). In the female brain, saturation isotherms yielded dissociation constants (Kd) of 6.2 x 10(-10) and 4.5 x 10(-8) M and maximal binding (Bmax) of 2.9 and 8.4 fmol/mg protein for the high and low affinity binding sites, respectively, and in the male brain a Kd of 2.3 x 10(-9) M and a Bmax of 3.5 fmol/mg protein. Displacement studies indicated that in the female brain the binding of 125I-hGH was inhibited in a dose-dependent manner more potently by lactogenic than by somatogenic hormones. The rank order of potencies of these hormones to inhibit the binding of 125I-hGH was hGH > hPRL > rPRL > oGH > rGH. However, in the male brain the inhibition of 125I-hGH binding was found to be most pronounced by somatogenic hormones with the rank order of hGH > oGH > rGH > hPRL > rPRL. These findings indicate the presence of specific binding sites for hGH in the rat brain. The level as well as the properties of these sites vary in the two sexes, with higher levels in the female brain as compared to the male brain. Moreover, these sites display predominantly lactogenic characteristics in the female brain and almost exclusively somatogenic characteristics in the male brain.
Animals↗
Opioid receptors influence spinal cord electrical activity and edema formation following spinal cord injury: experimental observations using naloxone in the rat.
The possibility that opioid peptides participate in alteration of spinal cord conduction following trauma to the cord was investigated in a rat model using a pharmacological approach. Spinal cord injury was produced in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of T10-11 segments (2 mm deep and 5 mm long). Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. SCEP from both rostral and caudal segments consisted of a small positive peak followed by a high negative peak. Infliction of trauma in untreated rats resulted in an immediate depression of the rostral maximal negative peak (MNP) amplitude. This depression was long-lasting. Later, a significant increase in the latency of the rostral MNP amplitude occurred. Naloxone was administered in a high dosage (10 mg/kg, i.p.) to block mu-, delta- and kappa-opioid receptors 30 min before injury. This drug treatment inhibited the immediate post-injury decrease of the rostral MNP amplitude without any significant effect on latency changes. Measurement of water content in the traumatized spinal cord segment showed a significant reduction in the drug treated animals 5 h after trauma (71.46 +/- 0.54) as compared with untreated controls (74.65 +/- 0.76). However, 1 mg or 5 mg/kg dosages of the drug were not effective in reducing the SCEP changes or edema after injury. These results strongly suggest that blockade of kappa-opioid receptors with high doses of naloxone is important in reduction of trauma induced alteration of SCEP and edema formation in spinal cord injury.
Animals↗
Somatogenic and lactogenic binding sites in rat brain and liver: quantitative autoradiographic localization.
The distribution of somatogenic and lactogenic binding sites in female and male rat brain as well as in liver was studied by quantitative receptor autoradiography using 125I-human growth hormone (125I-hGH) as a ligand. Quantitative measurement of binding sites for 125I-hGH showed differences in the levels of these sites in the female and male brain and liver. Moreover, regional differences in the brain were also observed in each sex. In the female brain high levels of 125I-hGH binding sites were found in the choroid plexus. Intermediate levels were observed in the striatum, the hypothalamus and the hippocampus, whereas low levels of these sites were found in the central gray, the temporal, the piriform and the entorhinal cortices. In the male brain high levels of 125I-hGH binding sites were detected in the choroid plexus. Intermediate levels were observed in the parietal cortex, the hypothalamus and the hippocampus, whereas low levels were found in the tegmentum, the temporal cortex and the striatum. Quantification of 125I-hGH binding sites in the liver revealed higher levels in the female than in the male liver. In general, higher levels of binding sites (16%-77%) were observed in the female than in the male tissues. The quantification of rat growth hormone (rGH) by radioimmunoassay was also performed in this study. Varying amounts of rGH immunoreactivity were detected in the different brain regions, with the highest levels of rGH-like material being found in the midbrain and cortex of both sexes. Moreover, higher levels of rGH-like material were observed in the female than in the male brain.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Spinal prodynorphin gene expression in collagen-induced arthritis: influence of the glucocorticosteroid budesonide.
Changes in the spinal expression of the opioid precursor and prodynorphin, which has been implicated in the response to peripheral inflammation, were examined with semi-quantitative in situ hybridization histochemistry in rats subjected to collagen II-induced arthritis. The effects of glucocorticosteroid treatment on the basal and inflammation-induced prodynorphin expression were evaluated. Collagen II-induced arthritis caused a 16-fold increase in prodynorphin mRNA levels which comprised all neurons expressing low levels under normal conditions. In the superficial dorsal horn, one group of neurons of a large size reacted with a dramatic increase of prodynorphin mRNA, while another group of small neurons exhibited a moderate elevation of prodynorphin mRNA levels. In the deep dorsal horn of arthritic rats, most prodynorphin neurons were large and showed high prodynorphin mRNA levels. Systemic treatment with the glucocorticosteroid budesonide attenuated the arthritis-induced increase of prodynorphin mRNA expression in a topospecific manner. The budesonide-induced reduction of prodynorphin mRNA levels was more pronounced in the deep dorsal horn than in the superficial dorsal horn. Budesonide treatment of control animals caused a small, but significant increase in prodynorphin mRNA levels in the superficial laminae I/II without affecting prodynorphin mRNA levels in the deep dorsal horn. The degree of arthritis correlated closely with spinal prodynorphin mRNA levels. The tight correlation between severity of arthritis and prodynorphin mRNA levels in non-treated and corticosteroid-treated arthritic rats suggests that spinal prodynorphin expression is a good parameter for the evaluation of the influence of peripheral inflammation and of the efficacy of analgesic/anti-inflammatory drugs in its treatment. Opposite effects of budesonide on basal and inflammation-induced prodynorphin expression may involve a spinal site of action in addition to peripheral anti-inflammatory mechanisms. We suggest that the collagen II-induced arthritis in the rat is an excellent model for human rheumatoid arthritis allowing for the study of molecular plasticity of anti-inflammatory and anti-nociceptive drug action at different levels of the neuroaxis.
Administration, Topical↗
Characterization of growth hormone binding sites in rat brain.
The binding of 125I-labelled rat growth hormone (GH) to different areas in the brain was studied in male Sprague-Dawley rats. A high density of GH binding was found in the choroid plexus, hypothalamus, hippocampus, pituitary and spinal cord, whereas a lower binding density was observed in the cortex. Binding of the hormone to the various brain regions was age dependent. Binding was also dependent on time, pH and protein concentration. The binding affinity of the labelled hormone to choroid plexus was 4.3 per nmol/l and the binding capacity was 33.4 nmol/mg protein. The corresponding figures for binding of 125I-labelled GH to hypothalamus were 5.6 per nmol/l and 21.6 nmol/mg protein. By sodium dodecyl sulphate electrophoresis of the cross-linked hormone-receptor complexes, molecular weights of 60,000 and 61,000 were determined for the binding units in the choroid plexus and hypothalamus, respectively. It was further indicated that the binding unit for rat GH was distinct from that for prolactin.
Animals↗