Memantine for prevention of spinal cord injury in a rabbit model.

BACKGROUND: This study was conducted to investigate the effect of memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist, on the neurologic outcome of spinal cord ischemia after aortic occlusion. MATERIALS AND METHODS: New Zealand White rabbits were anesthetized and spinal cord ischemia was induced for 40 minutes by infrarenal aortic occlusion. Animals were randomly allocated to 3 groups. Group 1 (n = 8, control) received no pharmacologic intervention, group 2 (n = 8) received intra-aortic memantine infusion (20 mg/kg) after aortic crossclamping, and group 3 (n = 8) was treated with systemic memantine infusion (20 mg/kg) 45 minutes before aortic occlusion. Neurologic status was scored by the Tarlov system (in which 4 is normal and 0 is paraplegia) at 12, 24, 36, and 48 hours after the operation. Lumbar spinal root stimulation potentials and motor evoked potentials from lower limb muscles were monitored before, during, and after the operation. After the animals were killed, the spinal cords were studied histopathologically. RESULTS: All potentials disappeared shortly after aortic crossclamping. They returned earlier in both memantine-treated groups than in the placebo group. Histologic examination of spinal cords revealed a few abnormal motor neurons in memantine-treated rabbits but found extensive injury in the control group. At 12 hours the median Tarlov scores were 0 in the control group (group 1), 2 in the intra-aortic memantine group (group 2, P =.001 versus control), and 3 in the systemic group (group 3, P =.0002 versus control). At 24 hours median Tarlov scores were 0, 2.5 (P =.0002), and 4 (P =. 0002), respectively. Finally, at both 36 and 48 hours median Tarlov scores were 0, 3 (P =.0006), and 4 (P =.0002), respectively. CONCLUSION: Memantine significantly reduced neurologic injury related to spinal cord ischemia and reperfusion after aortic occlusion.

Nonlinear analysis of epileptic activity in rabbit neocortex.

We report on the nonlinear analysis of electroencephalogram (EEG) recordings in the rabbit visual cortex. Epileptic seizures were induced by local penicillin application and triggered by visual stimulation. The analysis procedures for nonlinear signals have been developed over the past few years and applied primarily to physical systems. This is an early application to biological systems and the first to EEG data. We find that during epileptic activity, both global and local embedding dimensions are reduced with respect to nonepileptic activity. Interestingly, these values are very low (dE approximately equal to 3) and do not change between preictal and tonic stages of epileptic activity, also the Lyapunov dimension remains constant. However, between these two stages the manifestations of the local dynamics change quite drastically, as can be seen, e.g., from the shape of the attractors. Furthermore, the largest Lyapunov exponent is reduced by a factor of about two in the second stage and characterizes the difference in dynamics. Thus, the occurrence of clinical symptoms associated with the tonic seizure activity seems to be mainly related to the local dynamics of the nonlinear system. These results thus seem to give a strong indication that the dynamics remains much the same in these stages of behavior, and changes are due to alterations in model parameters and consequent bifurcations of the observed orbits.

Sources of electric brain activity: intracortical current dipoles.

Intracortical evoked potentials after electrical stimulation of the optic nerve were simultaneously recorded from the different layers of the rabbit's visual cortex. The averaged potentials were subjected to current source density analyses. The results show that the first event after the stimulus is a current sink in layer VI according to the excitatory terminations of the specific afferent fibres of the geniculate body. Since the largest part of the specific afferents terminates in layers IV and V, the sink in those layers may be due to excitatory synaptic events there. The corresponding current sources are situated in the upper layers and are most probably passive sources due to the active sinks. This example demonstrates that the generation of intracortical electric potentials can be explained by vertically oriented current dipoles according to the anatomical peculiarities.

An approach to a synopsis of EEG parameters, morphology of brain convolutions and mental activities.

A method for the projection of EEG data on the brain surface is proposed. The EEG data are obtained during the performance of mental tasks and represented as probability maps of power and coherence changes with respect to the averaged EEG at rest. The morphological data are obtained from 3D reconstructions of the brain by means of serial slices provided by an MRI scanner. Before scanning the positions of the EEG electrodes were marked by dummy electrodes of plexiglass filled with a contrast medium. Changes of power are color-coded and entered at the respective electrode positions, changes of coherence between the respective positions. The applicability of this procedure in the fields of psychology, psychiatry and neurology is discussed.

Electrophysiological and morphological properties of rat motor cortex neurons in vivo.

This paper describes results obtained from intracellular recordings and stainings of motor cortex neurons in the rat in vivo. Rats were anesthetized with phenobarbital. Neurons were intracellularly recorded with micropipettes filled with K+-methylsulphate + 4% HRP in phosphate buffer (pH 7.4). Successful recordings and stainings were obtained from 31 neurons. Intracellular recordings were distinguished as either intrasomatic or intradendritic. Action potentials (APs) recorded from somata were distinguished by their fast hyperpolarizing afterpotential from those recorded within dendrites. Dendritic APs were broader and often followed by an afterdepolarization. The firing patterns elicited by depolarizing current pulses allowed to distinguish 3 groups of neurons. (a) Group A neurons with a moderate firing-rate of up to 17 APs during a 100 ms depolarizing current pulse of 3.5 nA comprised small and large pyramidal cells and one aspiny multipolar neuron, probably a large basket neuron. (b) Group B neurons generated bursts, which either occurred spontaneously or during low intensity current injection. These neurons were classified as small pyramidal neurons and spiny star cells. (c) Group C neurons had a firing rate 3 times as high as group A neurons. These neurons were small aspiny cells with radial dendritic fields, which were classified as local interneurons. Intradendritic recordings were characterized by the occurrence of broad APs, most likely generated within the dendritic tree. Intracellular current injections produced burst-like potentials consisting of several APs with different amplitude and duration. In 3 penetrations of one apical dendrite up to 4 neurons were stained. In these recordings APs activated by intracellular current injection were particularly broad (up to 40 ms). The results suggest that neuronal firing patterns observed in in-vitro neocortical slices are also observed in in-vivo conditions.

[Focal epilepsy: generation and spreading mechanisms in experimental conditions]. / Fokale Epilepsie: Generierungs- und Ausbreitungsmechanismen unter experimentellen Bedingungen.

This paper describes essential mechanisms underlying focal epileptic activity. Within the centre of an epileptic focus neurons display a characteristic phenomenon - the paroxysmal depolarization shift. This type of activity is partly caused by membrane-intrinsic mechanisms and also by postsynaptic excitation. Burster neurons seem to play a special role in this mechanism. Whereas the centre of an epileptic focus is distinguished by its massive excitation, the immediate surrounding are characterized by massive inhibitory phenomena ("epileptic inhibition"). The transition from interictal to ictal phenomena goes along with the spread of activity to adjacent neocortical areas. Experimental studies give strong evidence that this epileptic spread is dependent on neocortical anatomy.

High resolution multi-temperature sensors for biomedical application.

A temperature sensor array was designed in order to study local temperature variations and temperature gradients in biological samples. The sensor probe was inserted in the optical cortex of rabbits in order to study temperature changes during normal brain activity as well as under artificial ventilation conditions. Temperature sensitive areas of 0.14 mm x 0.1 mm are arranged in a row with interdistances of 0.4 mm yielding high spatial resolution. A temperature resolution of 0.1 mK and a 90% response time of maximum 3 milliseconds was obtained utilizing the high temperature dependence of 2%/K of the conductivity of vacuum evaporated germanium films. The sensor is passivated by a 1 micron thick PECVD-silicon nitride layer and can be placed on glass-, alumina- and polymer substrates. For brain tissue studies, in order to minimize tissue damage the temperature sensors were placed on a 0.1 mm thick needle-shaped glass substrate. A sensor element mounted on a glass substrate and immersed in water showed a self heating of less than 5 mK due to the applied measurement current of 2.1 microA.

Pathophysiological aspects of dysphoric states.

Dysphoric states have been of particular interest for a long time since they occur not only in patients with psycho-organic syndromes but also in those with manic-depressive disease. This paper discusses some aspects of dysphoria from the pathophysiological point of view. Data mostly derived from epileptic patients indicate the critical role the limbic system plays in the control of emotions. It is suggested that functional alterations within the limbic system and its manifold interconnections to other parts of the central nervous system are responsible for characteristic pathophysiological phenomena as, e.g., dysphoria.

Paroxysmal neuronal depolarizations in the rat motorcortex in vivo: intracellular injection of the calcium agonist BAY K 8644.

Epileptic activity was elicited in the rat's motor cortex by local application of penicillin. At the neuronal level it consisted of typical paroxysmal depolarization shifts. The calcium agonist BAY K 8644 was injected into neurons showing such a discharge pattern. The application of this drug increased amplitude and after depolarization of paroxysmal neuronal depolarizations.

[Music perception, EEG and musical training]. / Musikrezeption, EEG und musikalische Vorbildung.

Changes of EEG during listening to music were studied in two groups of probands, one of them with several years of training on a musical instrument. The EEG was recorded simultaneously from 19 electrodes (10:20 system) against connected ear lobe electrodes. One minute recording periods at rest before and after music were compared with a period of one minute recording during listening to music. 30 seconds of each of these recordings were studied by Fourier analysis. Averaged power and coherence spectra (between transversally adjacent electrodes and between electrodes on homologous regions of both hemispheres) were computed. Broad band parameters were chosen for 5 frequency bands between 4 and 32 Hz. Significant changes of the parameters were represented topographically. During listening to music, a significant reversible decrease of the parameters studied was found: in the musically trained group on both sides, but preponderantly on the right hemisphere, in the non-trained group almost exclusively on the left hemisphere. Moreover, in the trained group, the changes occurred more frequently and involved larger regions of the skull than in the untrained group. In addition, the first group had most changes in the frequency range between 18 and 24 Hz, the second group between 13 and 18 Hz. Finally, comparisons of the changes between the control period before music and music and those between the control period after music and listening to music led to additional conclusions on different strategies of the processing of musical information in musically trained and untrained persons.

On-going EEG in depression: a topographic spectral analytical pilot study.

Spontaneous EEG activities recorded with 19 electrodes (10-20 system) on the scalp were quantified by spectral analytical methods (power and coherence spectra) to reveal changes of power and coherence during different conditions (eyes closed/relaxed, eyes opened/relaxed, flicker stimulation, reading, listening to a story). Control subjects and depressive patients were compared. Power as well as coherence changes were found in all frequency bands. Changes in the organization of the EEG were found in different areas of both hemispheres. The EEG organization was different in control subjects and depressive patients, indicating different levels of vigilance and/or different cognitive strategies in verbal tasks in the two groups.

Penicillin-induced epileptic phenomena in the rabbit's neocortex I. The development of interictal spikes after epicortical application of penicillin.

In an attempt to elucidate the generation mechanisms underlying interictal spikes in the neocortex, the temporal development of spikes after the epicortical penicillin (PNC) application was studied. Field potentials (FP) were recorded simultaneously within the 6 neocortical layers with a multielectrode consisting of 16 contacts (10 X 10 micron 2) in a row at spacings of 150 micron. A one-dimensional current-source-density (CSD) analysis yielded the positions of current, sink and source densities, so that the different electrical events during a spike could be more accurately located within the different neocortical layers. After the epicortical application of PNC a typical succession of events, which underly the development of spikes, was observed. These events are similar in the visual and the motor cortex: immediately after the epicortical PNC application negative transients occur in the two uppermost cortical layers as well as within layers V to III. Due to the diffusion of the drug a characteristic succession of different processes takes place. Fully developed spikes show a typical configuration of sources and sinks, a moderate sink in layer V initiates a massive, double-peaked sink within layers II, III. This configuration of sinks suggests that some sort of triggering mechanism takes place. Since similar events are observed during interictal spikes in the visual and the motor cortex, neuronal structures common to both cortical areas are supposed to be responsible for the generation of PNC spikes.

Penicillin-induced epileptic phenomena in the rabbit's neocortex II. Laminar specific generation of interictal spikes after the application of penicillin to different cortical depths.

To elucidate the generation mechanisms of interictal spikes we analyzed the electrical events in the different layers of the rabbit's neocortex after application of penicillin to distinct cortical layers. Field potentials (FP) recorded simultaneously from all layers with a 16-fold micro-electrode-assembly were subjected to current-source-density analysis (CSD), which allows a more accurate description of local electrical events. To demonstrate the influence of neocortical architectonics on the generation of interictal spikes, 3 different areas-area occipitalis 1, precentralis 1 and 2, according to Fleischhauer et al., were studied. Interictal spikes develop regardless of the depth of PNC application. Moreover the appearance of spikes does not seem to depend exclusively on the diffusion of PNC into a distinct cortical layer (i.e. layers IV and V). The CSD analysis indicated that different generation mechanisms within the different cortical layers underly the spikes. According to CSD configurations maximum sinks occur at depths where the dendrites join closely to form bundles. This finding supports the importance of dendrites for the generation of interictal spikes. Finally, the distribution of CSD patterns is similar in all 3 neocortical areas studied, if PNC is applied to the same cortical depth.

Computer-assisted EEG topography as a tool in the evaluation of actions of psychoactive drugs in patients.

This paper summarizes a tentative application of EEG topography to the evaluation of the efficiency of psychoactive drugs. It shows that the spectral content of the EEG, recorded simultaneously at different locations according to the international 10-20 system, is a sensitive measure for the quantification of drug activity. Furthermore, coherence analysis reveals differences in the functional organization of the neocortex under neuroleptic drug therapy.

[Mechanism of the generation of evoked potentials in the rabbit neocortex]. / Generierungsmechanismen evozierter Potentiale im Neokortex des Kaninchen.

This paper describes the analyses of evoked potentials recorded in different neocortical areas (Area precentralis 1 and 2, occipitalis 1 and 2) and elicited by different stimulation techniques (antidromic stimulation of the pyramidal tract, electrical stimulation of thalamic nuclei, the optic nerve and finally random dot stimulation of the retina). Field potentials were recorded intracortically with a 16-fold electrode. The analyses of field potentials with the current-source-density method yielded an estimation of the current source and sink density distributions within the six neocortical layers. Hence spatio-temporal patterns of layer specific activation processes (sinks and sources) can be described for the various evoked potentials. The results can be summarized as follows: every evoked potential shows a spatio-temporal pattern of sources and sinks which is independent of the neocortical area and the mode of stimulation. However, the late components of the evoked potentials show great variations in their generation mechanisms, thus indicating regional differences in neocortical architectonics. These observations are discussed with regard to morphology, electrical activity and functional properties of the studied neocortical areas.

The contribution of the cortical layers to the generation of the EEG: field potential and current source density analyses in the rabbit's visual cortex.

Intracortical spontaneous field potentials (EEG) were simultaneously recorded from the different layers of the rabbit's visual cortex using multielectrodes produced by thin-film technology. The signals were subjected to spectral analyses. Additionally, current source density analysis was applied to spontaneous delta waves. The results are based on 10 experiments. The spontaneous EEG of the rabbit's visual cortex consists mainly of slow delta waves. The spectral analytical studies of the delta band showed maximum power in layers I and II and in layers V and VI. Significant power minima were found in the middle layers IV and/or III. Essentially, the zones of power minima agree with the zones of minimum coherence and those zones where a phase reversal is observed. These properties of the intracortical spontaneous delta activity are best described as dipole-like. The spontaneous delta waves can be surface negative or surface positive; accordingly they show different source-sink distributions from which different generation mechanisms can be inferred. The possible mechanisms for the generation of these current source-sink distributions (dipoles) are discussed, taking into consideration the cortical anatomy. In many cases these discussions must be speculative because, for an unambiguous explanation of the observed phenomena, a much better knowledge of the cortical anatomy, the fibre connections with other cortical anatomy, the fibre connections with other cortical areas and with the deep cerebral structures is necessary.