Leao's Spreading Depression Research Articles

Amnesia global transitoria: una revisión. I. Aspectos clínicos

Transient global amnesia (TGA) is a neuropsychological syndrome in which a sudden, temporary loss of the capacity of creating new memories and a retrograde amnesia of variable intensity occur, whereas consciousness, personal identity and attention are preserved. To review different clinical aspects about TGA. Accordingly, the following topics will be reviewed: definition and diagnosis criteria, types of amnesias which should be ruled out and their peculiarities and differences with TGA, epidemiological data such as incidence, age, sex, educational level of the patients and number of TGA episodes, most frequent scene where TGA appears, and most common triggering events. Additionally, classical proposals about its possible etiology (epilepsy, vascular disease and migraine) and other new theories (Leao's spreading depression or influence of stress) will be revised. Finally, different data about neuroimaging studies in patients with TGA will be reviewed. There are data and arguments in favour and against the hypotheses regarding etiology of TGA, but there is no current consensus on a theory which explains in a satisfactory way the nature of this kind of amnesia.

Is Spreading Depression Bad for You?Focus on “Repetitive Normoxic Spreading Depression-Like Events Result in Cell Damage in Juvenile Hippocampal Slice Cultures”

In this issue of the Journal of Neurophysiology (p. x), Pomper et al. report that repeated episodes of spreading depression-like events (SDLEs) caused irreversible injury in hippocampal slice cultures taken from immature brains. Although after the first four or five SDLEs, antidromic population

Effects on locomotor activity after local application of (+)-UH232 in discrete areas of the rat brain.

The preferential dopamine autoreceptor, and slightly D3 preferring, antagonist (+)-UH232 (cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-dipropylamino) tetralin) increases locomotor activity and synaptic dopamine release in the nucleus accumbens and striatum after systemic administration to the rat. As shown in this study, (+)-UH232, was unable to produce an increase in locomotor activity measured for 60 minutes after local administration into the terminal or somato-dendritic regions of the mesolimbic dopamine pathways or into the lateral ventricle. Instead, a dose dependent decrease of spontaneous locomotor activity after local application (0.05-50.0 nmol/side) of (+)-UH232 into the nucleus accumbens, was seen. A similar reduction in locomotor activity was produced by the classical dopamine antagonist raclopride. Analysis of the dose*time interactions on locomotor activity did, however, indicate that there is a significant dose*time interaction after local application of (+)-UH232 into the lateral ventricle and VTA. Raclopride, on the other hand, produced only a weak time dependent effect in the VTA. The potential problem of Leao's spreading depression in micro-injection experiments were considered, however, spreading depression does not seem to influence the effects of (+)-UH232 locally applied into the nucleus accumbens. In conclusion, both (+)-UH232 and raclopride produced a dose dependent decrease in spontaneous locomotor activity when examined as the total activity count over 60 minutes after local application into the N Acc.

Re-entry waves of Leao's spreading depression between neocortex and caudate nucleus

About 40% of spreading depression (SD) waves elicited from the parieto-occipital cortex of anesthetised rats penetrated through the temporal lobe structures (amygdala) into the caudate nucleus. Almost 70% of these SD waves did not terminate in the caudate but returned to the cortex and spread through it toward the site of SD initiation. Longer cortico-caudate (5.9 ± 0.1min) than caudate-cortical (4.7 ± 0.2min) conduction times suggest that SD enters and leaves caudate through routes of different length. SD waves elicited by KCl microinjection into the caudate reached frontal and parieto-occipital cortical electrodes with latencies indicating that the transit point is 5 mm closer to the rostral than to the caudal electrode. The region best satisfying this condition corresponds to rostral claustrum. The directionally biased SD conduction through the transit zone provides a re-entry path for cortico-caudate-cortical SD propagation and forms thus a natural reverberator the small dimensions of which preclude generation of repetitive SD waves.

Potassium and calcium concentrations in interstitial fluid of hippocampal formation during paroxysmal responses.

The concentration of potassium ([K+]o) and of calcium ([Ca2+]o) in interstitial fluid of the hippocampal formation of rats anesthetized with urethan was recorded with double-barreled ion-selective microelectrodes. The ipsilateral angular bundle was stimulated with trains of repetitive pulses. [K+]o increased during angular bundle stimulation in both dendritic and cell body layers of the fascia dentata. When stimulation was frequent and intense enough to provoke intercurrent paroxysmal discharge (IPaD), [K+]o in the granule cell body layer rose much above the level it attained during previous, nonparoxysmal activation. No similar excess increase of [K+]o related to paroxysmal firing was observed in the dendritic layer. It is concluded that tonic paroxysmal discharge of the granule cells is associated with an outflow of K ions from the cell somata, but not the dendrites. Extracellular sustained potential (SP) shifts and responses of [K+]o associated with paroxysmal firing showed no consistent correlation in fascia dentata. It is concluded that paroxysmal SP shifts in fascia dentata (unlike in spinal cord and cerebral neocortex) are dominated by the extracellular currents generated by granule cells, not by neuroglia. In the postparoxysmal phase, however, a small residual SP shift was observed in both soma and dendrite layers, which had characteristics compatible with its being generated by glial cells. Responses of [Ca2+]o varied from rat to rat. During nonparoxysmal excitation [Ca2+]o increased, decreased, or remained unchanged. During paroxysmal firing [Ca2+]o always decreased in the granule cell body layer, but the magnitude of the response varied greatly. In the dendritic layer a similar but smaller decrease was observed in some but not all cases. Probable reasons for the unpredictability of the responses of [Ca2+]o are discussed. The responses of [Ca2+]o recorded in fascia dentata of urethan-anesthetized rats that have previously been kindled were not detectably different from those of control animals. Leão's spreading depression (LD) was associated with large increase of [K+]o, decrease of [Ca2+ )o, and intense negative SP shift in both dendritic and cell body layers of fascia dentata, as well as in CA1 zone of hippocampus. It is concluded that LD in hippocampal formation is associated with more widespread depolarization of pyramidal and granule cells than in cerebral neocortex and cerebellar cortex where changes of [K+]o are limited to the more superficial layers.

Leao's spreading depression: Synaptic regulation of a diffuse self-oscillating process in the central nervous system

The evidence reviewed in the paper shows that the spreading depression (SD) belongs to the mass of closely packed neurons which can support qualitatively new phenomena occurring at a more primitive level of cellular interaction. The latter becomes prepotent under extreme conditions, overloading the local energy supply and homeostatic mechanisms. The two levels of neural integration, the highly heterogeneous specifically connected synaptic level and the statistically uniform diffusively organized nonsynaptic level, are always present in all forms of brain activity and mutually influence each other. While phenomena mediated by nonsynaptic interaction overrule the synaptic ones under resting conditions, excessive synaptic excitation may either switch the affected brain region from synaptic to nonsynaptic interaction (spike-triggered SD) or assert the synaptic interaction over the nonsynaptic one (functional blockade of SD). Nonsynaptic interaction is an inherent property of brain, an obligatory consequence of the trade-off between maximal packing density and independent function of individual elements of the system which sets definite limits to the maximum activation of synaptic processes, contributes to slow synchronization of neural populations and plays an important role in various instances of brain pathology. The phenomena generated at this level belong to the family of autowaves, share their typical properties and can be described by similar formal rules.

Book Review: The Mechanism and Application of Leao's Spreading Depression of Electroephalagraphic Activity

Book Review: The Mechanism and Application of Leao's Spreading Depression of Electroephalagraphic Activity

Leao's spreading depression in the cerebellum of rat.

Ischämie ruft in der Kleinhirnrinde eine ähnliche Depolarisation hervor wie in der Grosshirnrinde. Durch lokale KCl-Applikation erhält man in der Kleinhirnrinde langsame Potentialwellen, die in Amplitude und Ausbreitungsgeschwindigkeit der «spreading depression» vonLeão in der Grosshirnrinde entsprechen. Ischämie und lokale Applikation von 2,4-Dinitrophenol bewirken in beiden Rindengebieten gleiche Verschiebungen der Kaliumionen.

On the conditions for the recording of Leao's spreading depression

The following requirements for the optimal recording of Leão's depression were discussed. (1) The corticogram should be led off bipolarly. (2) The distance between the members of each electrode pair should be small. For the rabbit 3 to 4 mm. is the maximum distance for recording complete depression. (3) The leading off conditions should be such that the electrodes pick up only the potentials from their immediate vicinity. When any one of these requirements is not met, the depression may not be seen on the EEG record. It seems possible that in some species the geometry of the cortex and the dimensions of of the overlying structures are such that the above conditions cannot be fully met. Leão's depression is accompanied by a, usually biphasic, slow potential change which precedes the start of the depression by 10 to 40 sec. When the leading off conditions are such that the depression cannot be recorded, this slow potential change may indicate the presence of the mechanism underlying the spreading depression.