Meike Wiedemann

Effects of antimigraine drugs on retinal spreading depression

It has been suggested that spreading depression may play a role in triggering classical migraine. In this study the retinal spreading depression was used as a pharmacological tool to test the neuronal effects of several common antimigraine drugs. As the chicken retina is void of any blood vessels the observed effects must be of pure neuronal origin. It is shown that propranolol, sumatriptan, methysergide, paracetamol and acetylsalicyclic acid decrease the propagation velocity of retinal spreading depression waves, accelerate the recovery of the optical and electrical signal and reduce the amplitude of the negative potential shift, concomitant with the spreading depression. Barbiturate increases the spreading velocity, and the amplitude of the potential shift. Ergotamine, clonidine, lisuride and iprazochrome have no significant influence on retinal spreading depression.

Gravity dependence of waves in the retinal spreading depression and in gel type Belousov–Zhabotinsky systems

In this study the influence of gravity on the velocity of propagating waves in excitable media was investigated in the retinal spreading depression (SD) and in gels of the Belousov–Zhabotinsky (BZ) reaction. It is assumed that in both systems diffusion and convection is small. Compared with liquids, convection in a gel should be absent or should be a much less efficient mode of heat and mass transport. Diffusion, though present in a gel, is slower than in a liquid. Nevertheless in both systems gravity dependent effects were found, including even effects in the case of when the g-vector is oriented perpendicular to the plane in which the waves propagate.

Control of the excitability of neuronal tissue by weak external forces

The spreading depression (SD) is a pronounced example of excitation-depression waves in excitable media, to which neuronal tissue according to its structure and functions belongs. SD waves can especially easily be observed in the vertebrate retina which is neuronal tissue and a true part of the central nervous system (CNS). According to the high intrinsic optical signal (IOS) concomitant with the retinal spreading depression (rSD), it can be monitored with standard video imaging techniques, thus the retina has been used in our studies as a suitable model system for neuronal tissue in general. In particular, the control of wave set-up and propagation in excitable media by weak external forces is of high interest. Accordingly, the interaction of rSD waves with DC and AC electromagnetic fields of low amplitude and frequency and with gravity has been investigated in this study. The dependence of rSD-wave propagation velocity on the given parameters as one important indication of excitability control has been investigated in detail. Our results with rSD waves are partially compared to another well known excitable medium, the Belousov-Zhabotinsky reaction, where some data about the effects of electrical fields and gravity have already been published.

Self-organization and Pattern-formation in Neuronal Systems Under Conditions of Variable Gravity

Nonlinear Physical Science is a new book series co-published by Higher Education Press of China (HEP) and Springe. This book series will provide a forum to systematically summarize recent developments, discoveries and progresses on Nonlinear Physical Science for historical records. The aims of the book series are to provide the fundamental and frontier theories and techniques for nonlinear physical science; to stimulate more research interest on nonlinearity, synchronization and complexity in nonlinear science; and to directly pass the new knowledge to the young generation, scientists, engineers and students in the corresponding fi elds.

The chicken retina as an experimental model for investigation of central nervous lesions

The aim of this study was to establish an experimental model to investigate neuronal lesions. The retina is an easy accessible model system to study central nervous system (CNS) disorders or neuronal effective drugs. It consists of only a few characteristic layers and is easy to prepare as an intact piece of tissue. In the retina the typical cell swelling of a developing lesion is accompanied by a very strong intrinsic optical signal (IOS) which is simultaneous with the electrical signal and is based on changes in light scattering. The IOS can be easily observed during the whole experiment and can be recorded with non-invasive optical methods for further quantification of damage. In the developed model, the lesions are elicited electrically with a tungsten microelectrode (0.1 M[omega]). The degree of damage depends on the magnitude of the stimulus. The parameters for the quantification of damage are the area and the brightness of the affected tissue. The growth of the lesions can be influenced with drugs added to the perfusion system. In the present study we tested, glycerol, mannitol and ketamine which are known to be neuroprotective in other animal models.

Exogenous application of gangliosides changes the state of excitability of retinal tissue as demonstrated by retinal spreading depression experiments

Abstract Gangliosides are amphiphilic, sialic acid-containing glycosphingolipids which are found preferentially in complex composition in the cellular membranes of the nervous system of vertebrates, including the vertebrate retina as well as in other membranes. They are always exposed to the extracellular side of the membranes. By virtue of the negative charges they carry at their headgroup, they contribute to the surface charge of the membrane and may affect ion distribution, mainly that of protons and calcium ions, at the outer side of the membranes. Using retinal spreading depression (RSD) as a tool, we show in this study that the addition of exogenous gangliosides to the extracellular space can change the state of excitability of the retinal tissue. In RSD experiments it reduces the propagation velocity as well as the intrinsic optical signal of RSD waves. These effects are concentration dependent (IC50 about 20 μM) and increase with the increasing negative charge of the ganglioside headgroup. As a possible mechanistic basis of the changes found, the change of the calcium homeostasis of the extracellular space by the exogenously added gangliosides is discussed. Gangliosides have been reported to be useful in the treatment of some neuropathological syndromes, including migraine, although experimental verification has not been possible up to now. Taking into account that the retina is a true part of the CNS, our data may be interpreted as the requested verification.

Microgravity dependence of excitable biological and physicochemical media

Summary.Neuronal tissue and especially the central nervous system (CNS) is an excitable medium. Self-organisation, pattern formation, and propagating excitation waves as typical characteristics in excitable media consequently have been found in neuronal tissue. The properties of such phenomena in excitable media do critically depend on the parameters (i.e., electromagnetic fields, temperature, chemical drugs) of the system and on small external forces to which gravity belongs. The spreading depression, a propagating excitation depression wave of neuronal activity, is one of the best described of the those wave phenomena in the CNS. Especially in the retina as a true part of the CNS it can be easily observed with optical techniques due to the high intrinsic optical signal of this tissue. Another of such waves in neuronal tissue is the propagating action potential in nerve fibres. In this paper, data from our laboratories concerning the influence of gravity on the velocity of propagating waves in excitable media are summarized mainly in terms of the retinal spreading depression and propagating action potentials. Additionally, we have used waves in gels of the Belousov–Zhabotinsky reaction as the physicochemical model system of biological activity as the properties of these waves follow the same theories as the spreading depression and action potentials and they have some striking similarities in wave behavior. Thus propagating Belousov–Zhabotinsky waves are described by their gravity dependence.

Biphasic effects of melatonin on the propagation of excitation waves in the chicken retina.

The retinal spreading depression (SD) is a propagating wave in an excitable medium, the neuronal tissue of the retina. Its velocity is about 3 mm/min and it is accompanied by a variety of changes in the tissue, including electrical and optical events. The pronounced intrinsic optical signal (IOS) of the retinal SD makes it an extremely versatile tool for the investigation of the action of drugs on neuronal tissue and more specific on propagating excitation waves in neuronal tissue. Furthermore, in the last decade increasing evidence has been collected, which shows that SD waves are the basic mechanism of the aura in classical migraine. We have investigated the influence of melatonin on the propagation of retinal SD waves as it has been postulated to have protective effects on neuronal tissue. The results demonstrate that melatonin indeed slows down the retinal SD, however, only in a defined concentration range. Additionally, it changes the IOS of the wave.

Behavior of Action Potentials Under Variable Gravity Conditions

The functional properties of neuronal tissue critically depend on cellular composition and intercellular communication. A basic principle of such communication found in various types of neurons is the generation of action potentials (action potentials) as discussed in Chapter 3 in some detail. These action potentials depend on the presence of voltage gated ion-channels (Fig. 7.1), especially sodium- and potassium channels, and propagate along cellular processes (e.g. axons) towards target neurons or other cells. It has already been shown in a previous chapter that the properties of ion-channels depend on gravity. To discover whether the properties of action potentials also depend on gravity, we examined the propagation of action potentials in earthworms (invertebrates) and isolated nerve fibers (i.e. bundles of axons) from earthworms under conditions of micro-and macro-gravity. In the second set of experiments we could verify our results on rat axons (vertebrates). Our experiments carried out during two parabolic flight campaigns revealed that micro-gravity slows action potential propagation velocity and macrogravity accelerates the transmission of action potentials. Additionally we looked at the behavior of spontaneously spiking neurons from leech in drop-tower experiments. The relevance of action potential behavior especially under microgravity for life science related questions is considerable, taking into account that altered gravity conditions might affect action potential velocity in man during space flight missions.

Interaction of Gravity with Molecules and Membranes

The basic to all ideas how gravity might interact with neuronal tissue is the cellular membrane being intrinsic part of any cells. It is known to be, with all its components and interactions, involved in all sensory processes. Ion-channels as integral membrane proteins are involved significantly in these mechanisms, and according to the question of gravity sensitivity they are of high interest based on two possible aspects. First, it might be possible that gravity directly interacts with single membrane based on proteins, including ion-channels; second, gravity might change its parameters instead of interacting with the thermodynamical system membrane, and thus affect the properties of ion-channels incorporated in the membrane indirectly. Changing physical parameters other than gravity in a variety of different experiments, for example temperature or pressure, has shown both mechanisms to be possible using a variety of techniques. Especially the investigation of mechano-sensitive ion-channels has contributed a lot to the understanding of how membranes can interact with mechanical and other weak external forces (i.e. Garcia-Anoveras and Corey, 1997; Sukharev, 1999).