Vera Maura Fernandes de Lima

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.

Effects of nitric oxide on the retinal spreading depression.

The retinal spreading depression has been used as a tool to investigate the action of nitric oxide (NO) as a diffusible neurotransmitter which in many cases acts by raising the cGMP level in target cells. The role of NO as a vasodilating agents has been well-established and it has been suggested that the vasodilatation concurrent with cortical SD may be mediated by NO. In this study, we present pure neuronal effects of NO on SD as the chicken retina is void of bloodvessels. We show that NO directly decreases the velocity of retinal SD waves in a concentration-and time-dependent manner. This effect can be partially mimicked by application of membrane-permeable cGMP derivatives. Furthermore, a NO-mediated speed up of the recovery of the intrinsic optical signal after the wave-front is shown.

Excitation waves in central grey matter: the retinal spreading depression

Abstract This review deals with a phenomenon which, although it has been known for five decades, has not been recognized until recently as a suitable tool for investigations of neuronal-glial interactions and the interesting consequences of the non-linearities arising from these cooperative effects, such as the transition from quiescent states to the propagation of excitation. For neurophysiologists interested in the excitability control of neuronal populations, the retinal spreading depression wave can also be very useful, especially as a basic model for epileptic activity triggering and propagation mechanisms. In the isolated eye cup, spreading depression waves (RSDs) can be observed with ease. In fact, the RSD wave can be seen with the naked eye, which gives the observer a complete and non-invasive two-dimensional view of propagation. In the intrinsic optical signal of the RSD, several components can be separated, either by their spectral preferences or by their temporal and spatial characteristics and experimental manipulations. Glial membrane channel activity and physical changes in the composition of the extracellular medium appear to the major contributions for the optical changes during RSDs. Different components are also found in the electrophysiological concomitants of the waves, some with neuronal (synaptic terminals) and some with glial predominance. Besides the clinical and physiological aspects, the RSDs are part of a general class of self-organizing spatiotemporal structures that arise in systems far from equilibrium known as dissipative structures. In the retina, low dimensional dissipative structures self-organized, self-sustained and spatially structured wave activity, can be maintained for hours either as a soliton ‘circling wave’ or as a complex sequence of interacting spirals. Therefore, the RSD can serve as a powerful tool for cross-disciplinary research in the field of non-linear dynamics.

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.

Central nervous tissue: an excitable medium. a study using the retinal spreading depression as a tool.

According to its physicochemical properties, neuronal tissue, including the central nervous system (CNS) and thus the human brain, is an excitable medium, which consequently exhibits, among other things, self-organization, pattern formation and propagating waves. Furthermore, such systems can be controlled by weak external forces. The spreading depression (SD), a propagating wave of excitation–depression, is such an event, which is additionally linked to a variety of medically important situations, classical migraine being just one example. Especially in retinal tissue, a true part of the CNS, the SD can be observed very easily with the naked eye and by video imaging techniques due to its big intrinsic optical signal. We have investigated the retinal SD and its control by external physical parameters such as gravity and temperature. Beyond this, especially due to its medical relevance, the control of CNS excitability by pharmacological tools is of specific interest, and we have studied this question in detail using the retinal SD as an experimental tool to collect information about the control of CNS tissue excitability.

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.

Extracellular matrix and its role in conveying glial/neural interactions in health and disease

We review the concepts and findings that may be related to the occurrence of non-linear glial/neural dynamics involving interactions between polyelectrolytes of the extracellular matrix and the basement membranes that cover the endfeet of glia at CNS interfaces. Distortions of perception and blocking of learning expressed in functional syndromes are interpreted as macroscopic electrochemical patterns that emerge in grey matter through glial/neural interactions.