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Biomedical subjects

A R Gardner-Medwin

Publications and source records attributed to A R Gardner-Medwin.

At least 19 recordsLinked to original sources
PubMed1991

Magnetic fields associated with spreading depression in anaesthetised rabbits.

Magnetic fields were measured with SQUID magnetometry outside the skull of anaesthetised rabbits during initiation and propagation of spreading depression (SD) in the cortex. Slowly changing fields (up to 1.4 pT) were observed during the propagation phase, from 4-8.5 min after initiation of SD with KCl application, with maxima at about 6 min. The peak amplitude of the equivalent net dipole generators in the brain was ca. 28 microA.mm, substantially less than previously observed with SD in vitro, but large enough that similar signals might be detectable in man.

Anesthesia, General↗
PubMed1989

Doubly modifiable synapses: a model of short and long term auto-associative memory.

Synapses that can be strengthened in temporary and persistent manners by two separate mechanisms are shown to have powerful advantages in neural networks that perform auto-associative recall and recognition. A multiplicative relation between the two weights allows the same set of connections to be used in a closely interactive way for short-term and long-term memory. Algorithms and simulations are described for the storage, consolidation and recall of patterns that have been presented only once to a network. With double modifiability, the short-term performance is dramatically improved, becoming almost independent of the amount of long-term experience. The high quality of short-term recall allows consolidation to take place, with benefits from the selection and optimization of long term engrams to take account of relations between stored patterns. Long-term capacity is greater than short-term capacity, with little or no deficit compared with that obtained with singly modifiable synapses. Long-term recall requires special, simply implemented, procedures for increasing the temporary weights of the synapses being used to initiate recall. A consolidation algorithm is described for improving long-term recall when there is overlap between patterns. Confusional errors are reduced by strengthening the associations between non-overlapping elements in the patterns, in a two-stage process that has several of the characteristics of sleep.

Association Learning↗
PubMed1988

Some possible neurological applications of applied potential tomography.

The applicability of applied potential tomography (APT) to imaging neuronal discharge and spreading depression in the brain has been assessed with single channel impedance measurements. Stimulation of frog sciatic nerve, rat cortex and human subjects produced no changes in impedance measured at 50 kHz greater than 0.02%, which suggests that APT systems currently in use could not image neuronal discharge in practice. Larger changes in impedance of about 40% during spreading depression could be reproducibly measured on rat cortex, and could be simulated by a mathematical model. The signal was attenuated but detectable when measured on the dura and outside the skull. Spreading depression could provide a useful model for the development of APT in the brain, which, if achievable, could lead to applications of clinical value in neurology and neurosurgery.

Animals↗
PubMed1987

The influence of hypocarbia on the resolution of transient increases in brain extracellular potassium.

The effect of acute hypocarbia on baseline extracellular K+ concentration [( K+]e) and its effect on the ability of the cerebral microenvironment to recover from transient increases in [K+]e has been assessed in rats. Spreading depression of cortical activity was used to present a reproducible K+ load to the extracellular space. Baseline [K+]e and the half-time for resolution of the [K+]e changes seen with spreading depression waves were measured for the hypocarbic and normocarbic states by means of double-barrelled K+ microelectrodes placed approximately 400 micron below the cortical surface. Three spreading depression waves were initiated in each animal for the two CO2 states. In group 1 (n = 10), the rats were initially normocarbic (PaCO2 41.6 +/- 3.0 mmHg; mean +/- SD), then hypocarbic (PaCO2 19.0 +/- 2.5 mmHg) for the second series of measurements. The baseline [K+]e was significantly higher in the normocarbic state 3.4 +/- 0.4 versus 3.0 +/- 0.4 mM l-1, P less than 0.01 (paired t test). During normocarbia, the K+ load (delta[K+]e) presented to the extracellular space following spreading depression was 49.4 +/- 7.5 mM l-1, n = 10 (peak [K+]e - baseline [K+]e). The half-time for resolution of the presented [K+]e load was 24.3 +/- 6.1 s. Following hypocarbia of 1.4 +/- 0.6 h, there was no change in delta[K+]e (49.0 +/- 6.0 mM l-1) but resolution t1/2 had increased to 35.8 +/- 11.2 s, P less than 0.01 paired t test.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1986

A new framework for assessment of potassium-buffering mechanisms.

A new concept, that of "buffer capacity," is defined for potassium-buffering mechanisms in neural tissue. Buffer capacities for different mechanisms can be added and compared, thus simplifying quantitative assessment of diffusion, cytoplasmic uptake, and spatial buffering under varied conditions. The characteristic frequency components for potassium disturbances due to neural events are identified. The effect of buffering by a reservoir of fluid at a tissue surface is analyzed, together with its intrinsic limitations. The role of retinal Müller cells in spatial buffering is considered quantitatively: both buffering to the tissue surface and buffering sideways through cell-to-cell connections.

Animals↗
PubMed1983

The effects of carbon dioxide, oxygen and pH on spreading depression in the isolated chick retina.

In the isolated chick retina, the propagation velocity of Spreading Depression (SD) was approximately doubled and the frequency of spontaneous waves was substantially increased with solutions bubbled with 5% CO2 instead of air, at constant pH (7.5-7.6). There was no effect on SD of raised pO2. Large changes of pH (to 6.4 and 9.4) produced, respectively, decreases and increases of velocity; but there was no clear pH dependence with changes less than 0.5 pH units. The resting [K+]0 and the elevation during SD, measured with K+ sensitive micro-electrodes, were not consistently altered with 5% CO2 when there was faster conduction. The effect of raised pCO2 is opposite to that observed previously in rat cortex in vivo, which afforded evidence for a similarity between SD and the disturbance in the aura phase of migraine attacks. The effects in vivo must presumably be due to factors not acting in the isolated chick retina.

Animals↗
PubMed1983

A study of the mechanisms by which potassium moves through brain tissue in the rat.

The flux of K+ produced by electric current across the pia-arachnoid surface of the neocortex of anaesthetized rats has been studied with K+-selective electrodes in a cup at the surface and with flame photometry. The potential differences developed across three regions of the rat brain (neocortex, cerebellum, hippocampus) have been measured as [K+] was altered in fluid at the surface. The experimental results have been related to those that would be expected (i) if K+ moved principally by diffusion in extracellular space and (ii) if current flow through cells makes a significant contribution to K+ transfer. K movement produced by current across the neocortical surface accounted for 0.06 of the transfer of electric charge with small currents in either direction (ca. 5 microA mm-2) and with larger currents out of the tissue. Large currents (ca. 20 microA mm-2) into the tissue produced less K+ movement, but still more than the fraction 0.012 expected for purely extracellular flux. Alternating current pulses (5 Hz) with zero net transfer of charge produced no flux of K+ across the surface, while alternation with unequal durations produced the same effects as the equivalent steady charge transfer. The K+ flux lagged behind the onset and cessation of current with a time constant ca. 45 sec, approximately as expected from calculations with a model of the tissue. A surface-negative potential shift averaging 2 mV was observed when [K+ ]at the brain surface was increased from 3 to 12 mM. The time for development of half of the full potential change was 20 sec, with the solution changes complete in less than 4 sec. These results are inconsistent with the hypothesis that K+ movement through brain tissue occurs principally through intercellular clefts, except where these movements involve very localized gradients. They are consistent with the conclusion that ca. 5 times as much K+ flux passes through cells (probably largely glial cells) as through extracellular space, with fluxes driven by either extracellular voltage or concentration gradients.

Animals↗
PubMed1983

Changes of extracellular potassium activity induced by electric current through brain tissue in the rat.

Ion-selective micro-electrodes have been used to measure K+ and Ca2+ activity changes in extracellular space beneath the surface of the neocortex and cerebellar cortex during current flow across the tissue surface in anaesthetized rats. Inward currents produced decreases of [K+]o and outward currents produced increases, with insignificant changes in [Ca2+]o. Changes of [K+]o were largest just under the surface of the tissue, but were detectable down to depths of ca. 1 mm. With appropriate sitting of electrodes in the cerebellar cortex, currents of 22 microA mm-2 for 400 sec produced changes averaging -42% for inward current and +66% for outward current. The [K+]o changes near the surface were most rapid immediately after the onset of current and more gradual after some tens of seconds. Deeper within the tissue the rate of change was more uniform and after the end of stimulation the return to base line was slower. The amplitude, depth dependence and time course of the [K+]o changes were in reasonable agreement with the results calculated for a model in which K+ moves partly through extracellular space but primarily through membranes and cytoplasm within the tissue. The [K+]o changes were not attributable to variations in neuronal activity, although unit activity could be modified by current, since alternating currents failed to produce [K+]o changes and neither 0.1 mM-tetrodotoxin nor 5 mM-Mn2+ abolished the changes. The [K+]o changes were not abolished by topically applied ouabain (4 X 10(-4) M), 2,4-dinitrophenol (20 mM) or iodoacetate (10 mM), or by asphyxiation. Consequently the [K+]o changes are not dependent on metabolism. The data suggest that there is a selective mechanism for passive K+ transport in an electrochemical gradient within brain tissue that results in higher K+ fluxes than could be supported by ionic mobility in the extracellular fluid. This mechanism exists not only at the surface but within the brain parenchyma and may involve current flow through glial cells.

Action Potentials↗
PubMed1983

Analysis of potassium dynamics in mammalian brain tissue.

Equations are derived for potassium (K+) dynamics in simplified models of brain tissue. These describe K+ movement in extracellular space, transfer of K+ associated with current flow through cells (the so-called spatial buffer mechanism) and equilibration between extracellular space and cytoplasm. Numerical calculations show that the principal data on K+ dynamics from various laboratories can be accounted for with simple assumptions about spatial buffer action and uptake. Much of the data is inconsistent with extracellular diffusion being the main mechanism for K+ flux through brain tissue, including some that has earlier been cited in support of this hypothesis. The buffering actions of spatial buffer transfer of K+ and of cytoplasmic equilibration, in which these mechanisms reduce rises of [K+]o that would otherwise occur, are analysed quantitatively for specific K+ source distributions and for spatial and temporal frequency components of general disturbances. Spatial buffer action has most effect in reducing [K+]o rises with net release over extensive zones of tissue (greater than ca. 200 micron in diameter) for periods of the order of minutes. Reductions greater than 75% may be achieved. With localized but prolonged release, the maximum [K+]o rise is little affected but the volume of tissue affected by more moderate rises is substantially reduced. Cytoplasmic K+ uptake also has most effect with widespread release, but its effect diminishes with prolonged periods of release. The effects of the buffering mechanisms and of K+ re-uptake into active neurones in determining the decline of [K+]o after a period of stimulation are considered. Re-uptake is unlikely to be the major factor responsible for [K+]o decline when this has a time course of only a few seconds. The properties necessary for the cells mediating the spatial buffer mechanisms, possibly glial cells, are assessed.

Animals↗
PubMed1981

Clearance of extracellular potassium: evidence for spatial buffering by glial cells in the retina of the drone.

Work with ion-selective microelectrodes on the retina of the honeybee drone has shown that potassium is released from photoreceptors during activity and enters glial cells. Measurements of the extracellular voltage gradients indicate that, in this preparation, currents flowing through the glial cells in the 'spatial buffer' pattern account for a large fraction of the glial K+ entry in the active region of the tissue.

Animals↗
PubMed1981

Possible roles of vertebrate neuroglia in potassium dynamics, spreading depression and migraine.

The membranes of glial cells are highly selectively permeable to potassium. The implications of this and the possible reasons for it are discussed. Glial cells may contribute to buffering the extracellular K+ concentration of brain tissue through several mechanisms. However, the only one that benefits from the K+ selective permeability is the so-called 'spatial' buffer mechanism, which acts more effectively than extracellular diffusion in many situations to speed the dispersal of local accumulations of potassium. The role of glial cells in buffering the extracellular K+ concentration may help to prevent the occurrence of a phenomenon called Leão's spreading depression (SD). A K+-induced K+ efflux from neurones, occurring when the EC K+ concentration rises above critical levels, is probably crucial in causing SD. The models that have been proposed to describe this process are discussed and related. Spreading depression is not known definitely to occur in man. It seems probable, however, that it occurs during attacks of 'classical' migraine, associated with neurological symptoms. These neurological symptoms have often been attributed to vasoconstriction rather than to SD since certain vasodilators can relieve the symptoms. Experiments with SD in anaesthetized rats show that at least one of these vasodilator interventions (administration of a CO2/O2 mixture) stops also the propagation of a wave of SD. This strengthens the evidence for a possible relationship between migraine and SD. The involvement of SD in migraine probably deserves more critical attention than has hitherto been devoted to it.

Animals↗
PubMed1980

[Studies on potassium transport through glial cell membranes (author's transl)].

The retina of the honeybee drone is used as a model for the study of ion movements across the membranes of the glial cells caused by changes in the extracellular potassium concentration. The values found for changes in extracellular potential suggest that at least some of the potassium that enters glial cells in an active region of tissue is associated with an efflux of potassium from parts of the glial syncytium not affected by an increase in extracellular potassium concentration. In addition, it appears that ions other than K+ cross the glial membrane.

Animals↗