Biomedical subjects

I A Langmoen

Publications and source records attributed to I A Langmoen.

At least 37 records · Page 2Linked to original sources

PubMed1996

Amino-acid release from human cerebral cortex during simulated ischaemia in vitro.

The aim of the present study was to investigate the release of amino-acids in human cerebral cortex during membrane depolarization and simulated ischaemia (energy deprivation). Superfluous tissue from temporal Iobe resections for epilepsy was cut into 500 microns thick slices and incubated in vitro. Membrane depolarization with 50 mM K+ caused a release of glutamate, aspartate, GABA and glycine, but not glutamine or leucine. The release of glutamate and GABA was Ca(++)-dependent. Slices were exposed to simulated ischaemia (energy deprivation; ED) by combined glucose/oxygen deprivation. This caused a Ca(++)-independent release of glutamate, aspartate, GABA, glycine, and taurine which started after 8 min, peaked at the end or shortly after the 27 min period of ED, and returned to control levels within 11 min following termination of ED. Preloaded D-[3H]aspartate was released both during K(+)-stimulation and ED. Release of D-[3H]aspartate during ED was delayed compared to glutamate supporting an initial phase of synaptic glutamate release. Uptake of L-[3H]glutamate was increased during the period of glutamate release, suggesting passive diffusion across the cell membrane or enhanced transport efficacy in cellular elements with functioning uptake mechanisms.

Amino Acids↗

PubMed1996

Cytotoxic effect of Ca++ released from intracellular stores during cerebral energy deprivation.

The increase in cytoplasmatic calcium concentration during cerebral ischemia has been proposed as a key event leading to neuronal death. In order to investigate a possible role of calcium-release from intracellular stores in ischemic neuronal injury, intracellular calcium pools were depleted prior to ischemia by the use of thapsigargin. Evoked activity (population spike) in rat hippocampal slices was monitored during a 30 min control period, 9 min of energy deprivation and 60 min of recovery. The population spike recovered to 27% (17-33) (median and 95% confidence interval) following energy deprivation in normal calcium, to 56% (50-58) in calcium-free incubation fluid and to 83% (75-88) in slices pretreated with 1 microM thapsigargin. Combining calcium removal and thapsigargin pretreatment did not improve recovery further. Both removal of extracellular calcium and emptying intracellular calcium stores prior to energy deprivation thus improved functional recovery following energy deprivation, however the latter was more effective. These results suggest that calcium release from intracellular stores may be of major importance in calcium-related neuronal injury during cerebral ischemia.

Action Potentials↗

PubMed1996

Release of brain amino acids during hyposmolar stress and energy deprivation.

The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or energy deprivation was measured by high-performance liquid chromatography. Exposing the slices to hyposmotic stress by lowering extracellular NaCl caused a 10-fold release of taurine (p < 0.01) and over a twofold increase of gamma-aminobutyric acid (GABA) and glutamate (p < 0.01). These changes were reversed by mannitol. Exposure to combined glucose and oxygen deprivation (energy deprivation) caused a 50-fold increase in the release of GABA, a 40-fold increase in glutamate release (p < 0.01), and a twofold to sixfold increase in taurine, aspartate, glycine, asparagine, serine, and alanine release (p < 0.05) but no change in glutamine. Energy deprivation increased the water content by 21%. Mannitol blocked this increase and further enhanced the release of glutamate and aspartate (p < 0.01) but not of GABA. The permissivity of the amino acids was plotted against the pI (pH at isoelectric point) and hydropathy indexes. Energy deprivation increased the permissivity in the following order: acidic > neutral > basic. Among neutral amino acids, permissivity increased with increasing hydrophobicity. These results indicate that the mechanisms of amino acid release are different during cerebral ischemia and hyposmotic stress.

Amino Acids↗

PubMed1995

Changes in amino acid release and membrane potential during cerebral hypoxia and glucose deprivation.

Excessive release of glutamate is believed to play a major role in the susceptibility of neurons to ischaemia. Whether the glutamate release is the primary event or occurs in response to electrophysiologic alterations has not been clarified. In the present study, the amino acid release was therefore correlated to changes in electrophysiological parameters and energy status during conditions of low oxygen tension and varying glucose concentrations in rat hippocampal slices. Plain hypoxia failed to produce glutamate release. All neurons underwent, however, a slow depolarization causing most of the neurons to lose their membrane potential within 10 minutes. By restoring the membrane potential to resting level by current injection, the neurons could still be activated synaptically and respond to transmitter application. Following reoxygenation most of the cells regained their resting membrane potential, but showed reduced excitability. When the slices were exposed to hypoxia combined with glucose deprivation (simulated ischaemia), there was a pronounced increase in the glutamate release. This glutamate release was always preceded by a fast anoxic depolarization. Whereas hypoxia reduced the ATP content only to approximately 50%, ATP was depleted in slices exposed to simulated ischaemia. The results demonstrate that although the neurons lose their membrane potential completely during hypoxia, there is no glutamate release. A fast anoxic depolarization provoked by simulated ischaemia, however, is always followed by glutamate release, probably due to a more severe ATP depletion.

Amino Acids↗

PubMed1995

Volatile anaesthetics: cellular mechanisms of action.

The mechanisms by which volatile anaesthetics act in the central nervous system are reviewed. The main cellular targets are excitatory synapses and the cell membrane of the neuronal cell body/dendrite, although there also appears to be a significant effect on thin unmyelinated fibres. Experiments quantifying these effects have shown that 1 MAC isoflurane reduces the activity in afferent fibres by 18%, excitatory synapses by 27% and postsynaptic neurones by 24%. Two important effects observed when recording from individual neurones are hyperpolarization of the cell membrane by an enhanced potassium conductance and increased threshold for initiation of action potentials. Excitatory synaptic transmission is most probably reduced due to a decreased release of transmitter from presynaptic terminals. Antagonistic and biphasic effects are often seen, for instance depression of both inhibitory and excitatory transmission and depolarization-hyperpolarization of the postsynaptic membrane.

Action Potentials↗

PubMed1995

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation.

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography. Hyposmotic stress induced a large release of taurine (25568 pmol mg-1 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity, blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg-1, respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary event, and increased amino acid formation likely secondary to this release.

Adenosine Triphosphate↗

PubMed1994

The effect of the volatile anesthetic isoflurane on Ca(2+)-dependent glutamate release from rat cerebral cortex.

A major effect of volatile anesthetics is to reduce excitatory synaptic transmission. In the present study the stimulated release of glutamate under the influence of increasing concentrations of isoflurane was studied in vitro by utilizing hippocampal slices from Wistar rats. Ca(2+)-dependent release was calculated by subtracting stimulated release with blocked synaptic transmission (50 mM K+, 0 mM Ca2+ and 4 mM Mg2+) from total evoked release (50 mM K+, 2 mM Ca2+ and 1 mM Mg2+). Isoflurane 0.5, 1.5 and 3% reduced Ca(2+)-dependent release of glutamate to 69, 58 and 49%, respectively (P < 0.05 for all related to control). These results are in agreement with the possibility of reduced release of transmitter as a mechanism of action of volatile anesthetics.

Animals↗

PubMed1993

Changes in evoked potentials and amino acid content during fluorocitrate action studied in rat hippocampal cortex.

Fluorocitrate inhibits the glial tricarboxylic acid cycle and thereby the synthesis of glutamine, which is the main precursor for transmitter glutamate. We investigated the possibility that there is a functional correlate to fluorocitrate action by recording evoked field potentials in rat hippocampal slices. The excitatory postsynaptic potential (field-EPSP) was markedly depressed after 7-8 h of fluorocitrate action. The population spike was also reduced, but a major part of the reduction may be the result of weaker synaptic activation rather than reduced excitability of the postsynaptic cells. The activity of thin unmyelinated fibres was only slightly affected. Preceding the changes in the field-EPSP there was a decrease in the glutamine content in the fluorocitrate treated slices relative to controls. Only a small decrease in tissue glutamate was seen concomitantly with the synaptic failure, probably because the transmitter pool of glutamate in those fibres stimulated makes little contribution to the total tissue glutamate.

Adenosine Triphosphate↗

PubMed1993

Redistribution of glutamate and glutamine in slices of human neocortex exposed to combined hypoxia and glucose deprivation in vitro.

This study was undertaken to elucidate the roles of neurons and glial cells in the handling of glutamate and glutamine, a glutamate precursor, during cerebral ischemia. Slices (400-600 microns) from human neocortex obtained during surgery for epilepsy or brain tumors were incubated in artificial cerebrospinal fluid and subjected to 30 min of combined hypoxia and glucose deprivation (an in vitro model of brain ischemia). These slices, and control slices that had not been subjected to "ischemic" conditions, were then fixed and embedded. Ultrathin sections were processed according to a postembedding immunocytochemical method with polyclonal antibodies raised against glutamate or glutamine, followed by colloidal gold-labeled secondary antibodies. The gold particle densities over various tissue profiles were calculated from electron micrographs using a specially designed computer program. Combined hypoxia and glucose deprivation caused a reduced glutamate immunolabeling in neuronal somata, while that of glial processes increased. Following 1 h of recovery, the glutamate labeling of neuronal somata declined further to very low values, compared to control slices. The glutamate labeling of glial cells returned to normal levels following recovery. In axon terminals, no consistent change in the level of glutamate immunolabeling was observed. Immunolabeling of glutamine was low in both nerve terminals and neuronal somata in normal slices and was reduced to nondetectable levels in nerve terminals upon hypoxia and glucose deprivation. This treatment was also associated with a reduced glutamine immunolabeling in glial cells. Reversed glutamate uptake due to perturbations of the transmembrane ion concentrations and membrane potential probably contributes to the loss of neuronal glutamate under "ischemic" conditions. The increased glutamate labeling of glial cells under the same conditions can best be explained by assuming that glial cells resist a reversal of glutamate uptake, and that their ability to convert glutamate into glutamine is compromised due to the energy failure. The persistence of a nerve terminal pool of glutamate is compatible with recent biochemical data indicating that the exocytotic glutamate release is contingent on an adequate energy supply and therefore impeded during ischemia.

Brain Ischemia↗

PubMed1993

Changes in inhibitory synaptic transmission induced by isoflurane studied in rat hippocampal slices.

The effect of isoflurane on inhibitory postsynaptic potentials (IPSPs) was studied in rat hippocampal slices by intracellular recordings from pyramidal neurons (n = 34). The amplitude of the IPSP was transiently increased and subsequently reduced in a dose-dependent manner. The duration of the IPSP was increased. The reduction in the IPSP persisted after correction was made for the anesthetic-induced hyperpolarization. The reversal potential for the IPSP was slightly displaced in the depolarizing direction. The depolarizing gamma-aminobutyric acid (GABA) response was unaltered, while the hyperpolarizing GABA response was reduced, suggesting a postsynaptic action. The reduction in the IPSP produced by isoflurane is at least partly due to an altered reversal potential for the IPSP (EIPSP).

Animals↗

PubMed1993

Epileptogenic effect of antibiotic drugs.

The epileptogenicity of antibiotic drugs represents a clinical problem, and it is well known that the use of penicillin and certain other preparations can induce seizures. In the present study, the authors investigated the epileptogenic properties of different concentrations of 12 commonly used antibiotic medications belonging to seven separate groups. The drugs were tested in the hippocampus, which has a low threshold for the development of epileptiform activity. The hippocampal slice technique, using rat tissue, was employed since absence of the blood-brain barrier allows administration of the drugs in known concentrations. The preparation was exposed to antibiotics in known concentrations and the amplitude and number of population spikes were recorded. Penicillin G was used as a reference substance. Cloxacillin (> or = 1 gm/liter), cephalothin (> or = 1 gm/liter), gentamicin (> or = 80 mg/liter), chloramphenicol (> or = 1 gm/liter), ciprofloxacin (> or = 50 mg/liter), erythromycin (> or = 1 gm/liter), and ampicillin (> or = 1 gm/liter) showed moderate to marked epileptogenic effects, whereas cefuroxime, clindamycin, cefotaxime, vancomycin, and tobramycin had no epileptogenic effects.

Aminoglycosides↗

PubMed1992

Calcium-dependent release of glutamate from human cerebral cortex.

The release of the excitatory amino acids glutamate and aspartate from human neocortex was investigated in vitro by utilizing brain tissue removed during anterior temporal lobectomies for tumor or epilepsy. Depolarization (50 mM K+) increased the glutamate release to 291% of control (809 pmol/mg/min) during blocked synaptic transmission and to 669% (1859 pmol/mg/min) when synaptic transmission was not blocked. Aspartate release increased to 141% (326 pmol/mg/min) and 178% (412 pmol/mg/min) respectively. The difference between release with and without blocked synaptic transmission was statistically significant only for glutamate (P less than 0.01). These data provides evidence for a Ca(2+)-dependent release of glutamate, supporting a possible role of this amino acid as a neurotransmitter in human neocortex.

Aspartic Acid↗

PubMed1992

Calcium dependent release of gamma-aminobutyric acid (GABA) from human cerebral cortex.

The release of the amino acids GABA, taurine, glycine, glutamine and leucine from human neocortex was investigated in vitro by utilizing brain tissue removed during 8 standard temporal lobectomies for epilepsy or tumor. Slices (0.5 mm thick) were cut from each biopsy and randomly placed in three different chambers. After 90 min preincubation, the three sets of slices were incubated for 60 s in wells containing, respectively, (A) regular ACSF (control), (B) ACSF with 50 mM K+ (to depolarize the cell membrane) and (C) ACSF with 50 mM K+, 0 mM Ca2+ and 4 mM Mg2+ (depolarization during blocked synaptic transmission). The content of amino acids in the wells was determined by high-performance liquid chromatography after pre-column derivatization of the amino acids with o-phthalaldehyde. Membrane depolarization (well B) increased the GABA release to 650% (620 pmol/mg) of control (well A, 95 pmol/mg). Blocking synaptic transmission (well C) reduced the evoked release by 50% (360 pmol/mg). The release of glycine, taurine, glutamine and leucine during membrane depolarization was not significantly different from the control values. The data provide evidence for a Ca(2+)-dependent release of GABA, supporting a possible role of this amino acid as a neurotransmitter in human neocortex.

Amino Acids↗

PubMed1992

Temperature sensitivity of thin unmyelinated fibers in rat hippocampal cortex.

The effect of changes in temperature on the activity of thin intracortical unmyelinated fibers was investigated in rat hippocampal slices. The amplitude of the presynaptic volley was increased by 40% when the temperature was raised from 23 degrees C to 30 degrees C, whereas the area of the presynaptic volley was reduced. Increasing the temperature above 30 degrees C was without further effect on the amplitude. The conduction velocity was 0.3 m.s-1 at 35 degrees C and 0.1 m.s-1 at 12 degrees C. The Q10 of velocity (25 degrees C-35 degrees C) was 1.6.

Animals↗

PubMed1992

Occurrence and management of fractured peripheral catheters in CSF shunts.

A series of 716 children underwent 2065 cerebrospinal fluid shunt procedures. Shunt failure due to fracture of the peripheral drain occurred 60 times, 38 times in ventriculo-atrial and 22 times in ventriculo-peritoneal shunts. The break occurred most commonly 2-4 cm above the neck incision in cardiac and just cephalad to the clavicle in abdominal drains. Fifty-nine ruptures occurred in Pudenz catheters (which were used in 82% of the shunts) and 1 occurred in a Holter drain (used in 17%). The fractured atrial catheters remained in situ (5/38) or were dislodged into the right cardiac ventricle (14/38), pulmonary arteries (9/38), right atrium (5/38) or hepatic veins (3/38). Two of the ruptured drains could not be located. Removal by a percutaneous transvascular snare technique was attempted in 27 cases and was successful in 24.

Adolescent↗

PubMed1992

An experimental study of the effect of isoflurane on epileptiform bursts.

The effect of isoflurane on penicillin- and picrotoxin-induced epileptiform activity was tested using hippocampal slice preparations. Isoflurane reduced both the frequency of spontaneous epileptiform bursts and the number of population spikes within each burst in a dose-dependent manner. The last population spikes in the burst were most sensitive to the anesthetic, whereas the first 4-6 spikes were quite resistant and persisted until spontaneous activity was abolished at 3% isoflurane. Isoflurane increased the stimulus current required to evoke epileptiform bursts and shifted the relationship between stimulus current and population spike amplitude to the right. At 3% isoflurane, a dose that usually causes iso-electric EEG and abolishes all spontaneous epileptiform activity, responses could still be evoked, and then invariably had an epileptiform pattern. The maximum response was reduced compared to control and 1.5% isoflurane. With isoflurane there was a reduced tendency for activity to be transmitted from one region within the hippocampus to the other. This effect was also dose-dependent. However, transmitted activity always retained a typical epileptiform character, although the number of population spikes within a train to some extent decreased with increasing concentrations of isoflurane.

Animals↗

PubMed1992

The effect of isoflurane on excitatory synaptic transmission in the rat hippocampus.

The purpose of this investigation was to study the effect of isoflurane on excitatory synaptic transmission. Rat hippocampal slices maintained in vitro were used as a model. Isoflurane caused a dose-dependent reduction of the excitatory postsynaptic potential (EPSP); 1.5% isoflurane reduced the EPSP by 35 +/- 9% (mean +/- s.d.) and 3% by 57 +/- 11%. Neither spontaneous nor potassium-stimulated efflux of the glutamate analogue D-(3H)aspartate was changed, but the content of D-(3H)aspartate in slices loaded during isoflurane was reduced to 83 +/- 12% of control (P less than 0.05). The intracellularly recorded response to direct application of glutamate increased by 37 +/- 20% during isoflurane (3%) and 50 +/- 5% during halothane (2%). Isoflurane (3%) enhanced the response to the glutamate receptor agonist quisqualate by 44 +/- 19%, whereas the N-methyl-D-aspartate response was unchanged. Isoflurane enhanced the tetanic depression of the population spike. The present results suggest that isoflurane reduces excitatory synaptic transmission by a presynaptic mechanism.

Animals↗

PubMed1991

Fatal cardiopulmonary complications in children treated with ventriculoatrial shunts.

During the years from 1965 to 1986, 716 children underwent a total of 2065 shunt procedures in our department. Of these, 1298 were ventriculoatrial (VA). Until 1979, Pudenz VA shunts were almost exclusively used as the primary procedure as well as in revisions. Since 1980, mini-Holter VA shunts have been implanted as a second choice, usually in cases with repeated distal failure in ventriculoperitoneal (VP) shunts. Observation time for children with VA shunts is therefore from 10 to 23 years for the great majority. The cumulative death rate for all patients is 24% (175/716), 9% (64/716) being tumor patients who eventually died as a result of their neoplasm. Most of the other deaths were caused by shunt infection or occurred in a group of children where shunts had been implanted for palliative reasons and where follow-up was only sporadic. Among the 450 children with VA shunts, 15 fatal complications occurred that were directly related to the atrial catheter, resulting in an accumulated incidence of 3% of such serious side effects from VA shunting. Three of these 15 fatal cases presented with nonspecific signs of cardiopulmonary failure following 10-21 years' shunting, and they died from irreversible pulmonary hypertension within a few months. A fourth case of late cor pulmonale has done unexpectedly well and has improved considerably while receiving anticoagulant therapy for over a period of 3 years.

Adolescent↗