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Biomedical subjects

M B Jørgensen

Publications and source records attributed to M B Jørgensen.

At least 19 recordsLinked to original sources
PubMed2001

Platelet serotonin transporters and the transporter gene in control subjects, unipolar patients and bipolar patients.

OBJECTIVE: The purpose of the present study was to relate the number of platelet serotonin transporters in unipolar and bipolar patients and in control subjects to two polymorphisms in the serotonin transporter gene: a VNTR in intron 2 and a deletion/insertion in the promoter region. METHOD: Density of platelet serotonin transporters was determined by radioligand binding analysis. Genotyping was performed by PCR amplification of polymorphic regions followed by size determination of the obtained fragments. RESULTS: The control subjects and the two groups of patients were similar with respect to the genotype and allele distribution belonging to the two polymorphisms in the serotonin transporter gene for. An interaction between status (control, unipolar- or bipolar patient) and VNTR genotype regarding the number of platelet serotonin transporters was observed; unipolar patients with the genotype 12/10 had more platelet serotonin transporters than bipolar patients and controls with this genotype. No association related to the polymorphism was found in the promoter region of the serotonin transporter gene. CONCLUSION: An association was observed between the polymorphism in intron 2 of the serotonin transporter gene and the number of platelet serotonin transporters. Unipolar patients with a particular genotype had more platelet serotonin transporters than the corresponding controls and bipolar patients.

Adult↗
PubMed2001

Post-traumatic stress disorder: a review of psychobiology and pharmacotherapy.

OBJECTIVE: To review the literature on the psychobiology and pharmacotherapy of PTSD. METHODS: Relevant studies were identified by literature searches (Pub-med, Web of Science) and through reference lists. The search was ended by May 2001. RESULTS: There is evidence of involvement of opioid, glutamatergic, GABAergic, noradrenergic, serotonergic and neuroendocrine pathways in the pathophysiology of PTSD. Medications shown to be effective in double-blind placebo-controlled trials includes selective serotonin reuptake inhibitors, reversible and irreversible MAO-inhibitors, tricyclic antidepressants and the anticonvulsant lamotrigine. Still more agents appear promising in open-label trials. CONCLUSION: The complexity of the psychobiology is reflected by the difficulties in treating the disorder. According to the present knowledge, suggestions for drug treatment of PTSD are made.

Glutamic Acid↗
PubMed1998

Middle ear transmission in the grass frog, Rana temporaria.

The anuran middle ear serves to transmit eardrum vibrations to the inner ear. In order to do this efficiently, the eardrum and middle ear must operate as an impedance transformer matching the low impedance of air to the higher impedance of the fluid-filled inner ear. In amniotes, one of the mechanisms used to achieve impedance transformation is to have the middle ear work as a force-amplifying lever system. Here, we present evidence that the grass frog middle ear also implements a lever system. The columellar footplate, which sits in the oval window, is firmly connected to the otic capsule along its ventral edge. Therefore, simple in-out movement of the columella is prevented while a rotational movement around the footplate's ventral edge is possible. The latter movement pattern was confirmed by laser vibrometry measurements of eardrum and footplate vibrations. The results showed that the footplate vibrations were 20-30 dB weaker than those of the eardrum and that the two structures vibrated 180 degrees out of phase (at low frequencies). The lever ratio was approximately 6, i.e. somewhat higher than lever ratios reported for amniotes. Hence, the middle ear lever probably makes a significant contribution to impedance matching in frogs.

Animals↗
PubMed1998

Basic response characteristics of auditory nerve fibers in the grassfrog (Rana temporaria).

Responses to free-field sound of 401 fibers from the VIIIth nerve of the grassfrog, Rana temporaria, are described. The spontaneous activities of the fibers ranged from 0 to 75 spikes/s, showing only weak correlation with frequency or sensitivity of the fibers. The highest spontaneous activities were approximately twice as high as reported previously for frogs. Best frequencies ranged from 100 to 1600 Hz and thresholds ranged from 21 to 80 dB SPL. The median dynamic range was 20 dB and the slopes of the rate-level curves ranged from 5 to 20 spikes/(s-dB). Most of the units showed post-excitatory suppression (PS) of their spontaneous activity. The duration of PS increased with sound level, also in fibers showing a decrease in firing rate at high intensities. Most fibers showing one-tone suppression did not show PS at their best suppression frequencies. Strong suppression was observed also in very phasic cells giving one spike per stimulation. Therefore, the mechanism underlying PS is probably different from that underlying adaptation. The sharpening of the neural encoding of temporal parameters and the strong encoding of sound offset as well as onset caused by PS very likely is biologically important.

Acoustic Stimulation↗
PubMed1997

Directionality of auditory nerve fiber responses to pure tone stimuli in the grassfrog, Rana temporaria. I. Spike rate responses.

We studied the directionality of spike rate responses of auditory nerve fibers of the grassfrog, Rana temporaria, to pure tone stimuli. All auditory fibers showed spike rate directionality. The strongest directionality was seen at low frequencies (200-400 Hz), where the spike rate could change by up to nearly 200 spikes s-1, with sound direction. At higher frequencies the directional spike rate changes were mostly below 100 spikes s-1. In equivalent dB SPL terms (calculated using the fibers' rate-intensity curves) the maximum directionalities were up to 15 dB at low frequencies and below 10 dB at higher frequencies. Two types of directional patterns were observed. At frequencies below 500 Hz relatively strong responses were evoked by stimuli from the ipsilateral (+90 degrees) and contralateral (-90 degrees) directions while the weakest responses were evoked by stimuli from frontal (0 degree or +30 degrees) or posterior (-135 degrees) directions. At frequencies above 800 Hz the strongest responses were evoked by stimuli from the ipsilateral direction while gradually weaker responses were seen as the sound direction shifted towards the contralateral side. At frequencies between 500 and 800 Hz both directional patterns were seen. The directionality was highly intensity dependent. No special adaptations for localization of conspecific calls were found.

Acoustic Stimulation↗
PubMed1997

Directionality of auditory nerve fiber responses to pure tone stimuli in the grassfrog, Rana temporaria. II. Spike timing.

We studied the directionality of spike timing in the responses of single auditory nerve fibers of the grass frog, Rana temporaria, to tone burst stimulation. Both the latency of the first spike after stimulus onset and the preferred firing phase during the stimulus were studied. In addition, the directionality of the phase of eardrum vibrations was measured. The response latency showed systematic and statistically significant changes with sound direction at both low and high frequencies. The latency changes were correlated with response strength (spike rate) changes and were probably the result of directional changes in effective stimulus intensity. Systematic changes in the preferred firing phase were seen in all fibers that showed phaselocking (i.e., at frequencies below 500-700 Hz). The mean phase lead for stimulation from the contralateral side was approximately 140 degrees at 200 Hz and decreased to approximately 100 degrees at 700 Hz. These phaseshifts correspond to differences in spike timing of approximately 2 ms and 0.4 ms respectively. The phaseshifts were nearly independent of stimulus intensity. The phase directionality of eardrum vibrations was smaller than that of the nerve fibers. Hence, the strong directional phaseshifts shown by the nerve fibers probably reflect the directional characteristics of extratympanic pathways.

Acoustic Stimulation↗
PubMed1996

Sound and vibration sensitivity of VIIIth nerve fibers in the grassfrog, Rana temporaria.

We have studied the sound and vibration sensitivity of 164 amphibian papilla fibers in the VIIIth nerve of the grassfrog, Rana temporaria. The VIIIth nerve was exposed using a dorsal approach. The frogs were placed in a natural sitting posture and stimulated by free-field sound. Furthermore, the animals were stimulated with dorso-ventral vibrations, and the sound-induced vertical vibrations in the setup could be canceled by emitting vibrations in antiphase from the vibration exciter. All low-frequency fibers responded to both sound and vibration with sound thresholds from 23 dB SPL and vibration thresholds from 0.02 cm/s2. The sound and vibration sensitivity was compared for each fiber using the offset between the rate-level curves for sound and vibration stimulation as a measure of relative vibration sensitivity. When measured in this way relative vibration sensitivity decreases with frequency from 42 dB at 100 Hz to 25 dB at 400 Hz. Since sound thresholds decrease from 72 dB SPL at 100 Hz to 50 dB SPL at 400 Hz the decrease in relative vibration sensitivity reflects an increase in sound sensitivity with frequency, probably due to enhanced tympanic sensitivity at higher frequencies. In contrast, absolute vibration sensitivity is constant in most of the frequency range studied. Only small effects result from the cancellation of sound-induced vibrations. The reason for this probably is that the maximal induced vibrations in the present setup are 6-10 dB below the fibers' vibration threshold at the threshold for sound. However, these results are only valid for the present physical configuration of the setup and the high vibration-sensitivities of the fibers warrant caution whenever the auditory fibers are stimulated with free-field sound. Thus, the experiments suggest that the low-frequency sound sensitivity is not caused by sound-induced vertical vibrations. Instead, the low-frequency sound sensitivity is either tympanic or mediated through bone conduction or sound-induced pulsations of the lungs.

Acoustic Stimulation↗
PubMed1996

One-tone suppression in the frog auditory nerve.

Sixty-seven fibers of a sample of 401 in the auditory nerve of grassfrogs (Rana temporaria) showed one-tone suppression, i.e., their spontaneous activity was suppressed by tones. All fibers were afferents from the amphibian papilla with best frequencies between 100 and 400 Hz. Best suppression frequencies ranged from 700 to 1200 Hz. Spontaneous activities for the fibers showing one-tone suppression ranged from 3 to 75 spikes/s. Spontaneous activities above 40 spikes/s and the phenomenon of one-tone suppression itself has not been reported previously for frogs. The population of fibers showing one-tone suppression comprises 81% of all fibers with best frequencies below 400 Hz and spontaneous activities higher than 3 spikes/s, indicating that the mechanism underlying the suppression is quite general.

Acoustic Stimulation↗
PubMed1995

Long-term decrease in the hippocampal [3H]inositoltriphosphate binding following repeated electroshock in the rat.

A quantitative autoradiographic study was made on the binding of the phosphatidylinositol system ligand [3H]inositol(1,4,5)-triphosphate (IP3) to forebrain sections from electroconvulsive shock (ECS)-treated rats. One group of rats was sacrificed 1 day and 1 month, respectively, after 12 ECSs administered three times weekly for 4 weeks. SHAM-stimulated rats served as controls. A single ECS did not change the [3H]IP3 binding in any of the brain regions examined. One day after the last of 12 ECSs, a decrease in [3H]IP3 binding (21%) was found within the CA1 region of the hippocampus and the piriform cortex (39%). In rats sacrificed 1 month after the last of 12 ECSs, the [3H]IP3 binding in piriform cortex had returned to control level. In the CA1 region of the hippocampus, the binding was still decreased (24%). It is possible that changes in the phosphatidylinositol system may play a part in the neurobiological events responsible for the therapeutic effect of electroconvulsive therapy.

Animals↗
PubMed1995

Treatment of traumatic effusion in the elbow joint: a prospective, randomized study of 62 consecutive patients.

Sixty-two patients with post-traumatic radiologically visualized effusion in the elbow joint, apparently without bony damage, were randomized to either 1 week of immobilization in a plaster or immediately instructed in active exercises without any immobilization. They were reexamined by an orthopaedic surgeon weekly until recovery. New radiographs were taken after 1 week. Reevaluation of the radiographs by a radiologist revealed seven 'false-positive' effusions, i.e. neither effusion nor fracture, and 21 missed fractures. All but five missed fractures, continued in the study. Thirty patients started immediate active exercises instructed by the surgeon and 27 were immobilized. The 'active exercise' group had a significantly shorter recovery time (one week vs two weeks, P < 0.05). The presence of missed fractures did not influence the result and all patients recovered fully. Also four of the excluded patients with missed fractures recovered fully. One patient with missed fracture dropped out from follow-up. We recommend that an apparently isolated post-traumatic effusion in the elbow joint is treated with immediate active exercises followed by a clinical reexamination after one week supplemented with new radiographs if there is unsatisfactory clinical progress.

Adolescent↗
PubMed1993

Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus.

By taking advantage of the specific neuronal and connective organization of the hippocampus and the different susceptibility of hippocampal neurons to transient cerebral ischemia or intraventricular injections of kainic acid (KA), we examined the microglial reactions to different types of neuronal injury. In all areas with neuronal or axonal degeneration, the microglial cells reacted by specific degeneration-related morphological transformations and expression of class I major histocompatibility complex (MHC) antigen. Subpopulations of microglial cells also expressed class II MHC antigen and leukocyte common antigen (LCA) in relation to (1) degenerating nerve cell bodies in the dentate hilus and the CA1 and CA3 pyramidal cell layers, (2) postischemic degeneration of dendrites in the stratum radiatum of CA1, and (3) combined dendritic and axonal degeneration in the stratum radiatum of the KA-lesioned CA3. MHC II and LCA expression was not observed in relation to degeneration of the CA3-derived Schaffer collaterals in CA1 after KA-induced CA3 lesions. In the case of ischemia the degeneration-related reactions were preceded by an early, generalized microglial reaction, which also included areas without subsequent signs of neural degeneration. This reaction, which was transient and characterized by subtle morphological changes and induction of class I MHC antigen only, was presumably triggered by a general postischemic perturbation of the cerebral microenvironment, and not by actual neural degeneration. In conclusion, we found that microglial expression of class I MHC antigen was a sensitive marker of both the general perturbation after ischemia and axonal degeneration distant from the areas of actual nerve cell death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus.

The aim of this study was to characterize the microglial and astroglial reactions to degeneration of (a) hippocampal CA1 pyramidal cells and dentate hilar neurons induced by cerebral ischemia and (b) CA3 pyramidal cells and dentate hilar neurons induced by intraventricular injections of kainic acid (KA). The microglial reactions to ischemia, as monitored by histochemical staining for the enzyme nucleoside diphosphatase (NDPase) and immunohistochemical staining for the complement type 3 receptor (CR3), could be divided into (1) initial and generalized, but transient, reactions which also included areas devoid of subsequent neural degeneration and (2) protracted, degeneration-specific reactions in the areas with neural degeneration. Due to more widespread hippocampal involvement a similar distinction was not possible after KA lesions. After both ischemia and KA application the protracted degeneration-specific reactions were characterized by increased NDPase/CR3 reactivity and prominent morphological changes. In the dentate hilus, reactive microglial cells clustered around the degenerating hilar neurons. In stratum radiatum of CA1, reactive microglial cells transformed into either (1) "rod cells," aligned along the postischemic, degenerating pyramidal cell dendrites, followed by subsequent transformation into ameboid-like cells, or (2) "bushy" cells, in response to degeneration of Schaffer collaterals induced by KA lesioning of CA3 pyramidal cells. Within stratum radiatum of the KA-lesioned CA3, where both dendrites and axons were degenerating, the microglial cells developed into stellate cells with thickened, retracted processes and plump cell bodies. These cells were supplemented by rounded macrophage-like cells. Astroglial reactions, monitored by immunohistochemical staining for the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin (VIM), and the normal plasma constituent immunoglobulin G (IgG), showed an initial and generalized astroglial immunoreactivity for IgG, which paralleled the initial and transient microglial reactions, while the reactive changes in GFAP and VIM immunohistochemistry paralleled the protracted, degeneration-specific reactions with regard to timing, strength, and distribution. In the KA-lesioned CA3, the most prominent finding was a prompt loss of astroglial GFAP immunoreactivity corresponding to the degenerating pyramidal cell layer and the adjacent mossy fiber layer. The results strongly indicate that stimuli other than neural degeneration initiated the activation of both microglial and astroglial cells, which then upon further activation by actual neuronal damage and degeneration adjust according to which neuronal structures were undergoing degeneration.

Acid Anhydride Hydrolases↗
PubMed1993

Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation.

There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1993

Nitric oxide does not act as a mediator coupling cerebral blood flow to neural activity following somatosensory stimuli in rats.

The possible role of nitric oxide (NO) on vibrissa-stimulated increase of regional cerebral cerebral blood flow (rCBF) and cerebral metabolic rate of glucose (rCMRglu) was investigated in conscious Wistar rats by using an inhibitor of NO synthase, NG-nitro-L-arginine (NOLAG) at a concentration of 30 mg/kg. In vivo autoradiography distribution with 14C-iodoantipyrine and 14C-deoxyglucose in two separate series showed CBF of 174% of control and CMRglu of 196% of control in the primary sensory cortex opposite the stimulated side in saline treated control animals. Similar increases were found in NOLAG-treated animals. Furthermore, NOLAG did not change either basal CMRglu or CMRO2. The findings suggest, that NO is not involved in coupling flow to the increased metabolism accompanying physiological sensory stimuli.

Animals↗
PubMed1993

Impairment of Fos protein formation in the rat infarct borderzone by MK-801, but not by NBQX.

In the present immunocytochemical study, we investigated the mechanism of Fos protein induction and the regional distribution of the Fos protein in brains of spontaneously hypertensive rats subjected to 2 h of permanent middle cerebral artery occlusion (MCAO). Rats were administered either saline or a glutamate receptor antagonist; the non-competitive NMDA receptor antagonist MK-801 or the AMPA receptor antagonist NBQX which are known to be able to reduce infarct size in MCA occluded rats. The saline treated rats showed presence of Fos protein in nerve cell nuclei throughout the cortical and striatal infarct borderzone, but no staining in the infarct core or contralateral hemisphere. MK-801 almost totally abolished this expression of Fos protein whereas NBQX had no significant effect on Fos protein expression. It is suggested that the Fos protein induction is due to repeated spreading depressions mediated by NMDA receptors in the infarct borderzone, and that Fos protein due to its persistence in the tissue can be used as a histochemical marker of borderzone tissue at risk for eventually becoming recruited in the infarct.

Animals↗
PubMed1993

The role of signal transduction in the delayed necrosis of the hippocampal CA1 pyramidal cells following transient ischemia.

A short period of cerebral ischemia leads to necrosis of the hippocampal CA1 pyramidal cells. Until recently no mechanisms contributing to this selective vulnerability were known. During the last decade an increasing amount of research has been concentrated on identifying signs of disturbed signal transduction in these neurons after ischemia. The present thesis is a review of these studies with some emphasis on my own contributions to the field. Gerbil and rat models of transient global ischemia are the most frequently employed. In order to produce the selective necrosis the main arteries to the brain are occluded for 5-20 minutes. In the rat it is often also necessary to lower the blood pressure. It takes 2-7 days of recirculation before the CA1 pyramidal cells become necrotic. The studies show that the necrosis can be attenuated or aggravated by drugs acting as inhibitors or enhancers of signal transduction--also if administered shortly after ischemia. The necrosis can be similarly influenced by lesions of excitatory or inhibitory afferent neurons. The protective effect of the lesion however, can be due to the lesion-induced decrease in metabolism. During ischemia there is an increase in the extracellular concentration of several excitatory and inhibitory neurotransmitters as well as in intracellular second messengers. Some of the latter also show an increase during recirculation. In vitro autoradiographic studies of receptor proteins show either unchanged or diffusely distributed downregulation of the ligand binding to the various extra- and intracellular receptor proteins following ischemia and early recirculation. A second decrease is seen in the CA1 at the time of and probably secondary to the necrosis. The IP3 receptor decrease appears during the first minutes of recirculation and lasts for up to 14 days. The protective lesion of the excitatory afferents from CA3 also leads to a decrease in IP3 binding. The changes in receptor regulation are not accompanied by increased postischemic electrophysiological activity in the CA1. In vivo autoradiographic mapping of the regional cerebral metabolic rate of glucose show increased metabolism in the CA1 during the first hour of recirculation compared to the rest of the brain were it is depressed. This relative hypermetabolism is not seen if the CA1 has been deprived of its primary source of excitatory afferents. A later secondary increase seen in the more or less necrotic CA1 pyramidal cell layer is probably due to macrophage activity. In situ hybridization and immunohistochemical studies on the expression of c-fos mRNA and protein respectively has been used to depict neurons with increased activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Drift barriers in the postcartilaginous development of the mammalian otic capsule.

Postcartilaginous development of the otic capsule was studied in undecalcified histological material from rabbits following sequential fluorochromic time labeling of mineralizing tissues, using combined microradiography, fluorescence microscopy and osteoid staining. Early fetal bone formation was monitored by labelling of the experimental animals in utero. In contrast to the normal pattern of drift movements displayed by long bones and extracapsular cranial bone, capsular bone inside a zone immediately surrounding the perilymphatic space developed as a separate functional unit in which growth and modeling was absent. Bone tissue behavior appeared to depend on its spatial relation to the membranous labyrinth rather than histological characteristics. These findings suggest the role of inner ear tissues as a functional matrix in control of capsular bone dynamics beyond fetal life.

Animals↗