Identifying essential conditions for refractoriness of Leão's spreading depression—Computational modeling

Teixeira, Hewerson Z.; Almeida, Antônio-Carlos G. de; Infantosi, Antonio Fernando Catelli; Rodrigues, Antônio Márcio; Costa, Natália L.; Duarte, Mario Antônio

doi:10.1016/j.compbiolchem.2008.03.011

Cited by 5 publications

(12 citation statements)

References 24 publications

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“…It was different from some previous theoretical work that addressed the characteristics of a solitary CSD wave [43][44][45]. Many experiments showed the inhomogeneous spatiotemporal evolution of successive CSD waves, but the modeling work on this issue was still few [32,33]. The present modeling has been successful in simulating the single or successive CSD waves.…”

Section: Discussionmentioning

confidence: 82%

“…Since the clinical relevance of CSD, there has been extensive interest in both experimental and computational aspects of CSD [6,13,32,[38][39][40][41][42]. This paper aimed to simulate the variation of repetitive CSD waves found in experiments with a computational study [18,25,27,28].…”

Section: Discussionmentioning

confidence: 99%

“…But the duration of the primary wave was similar to that of each succeeding CSD wave [24]. With careful inspection and calculation, a longer time interval after the last CSD would give birth to the following CSD with larger amplitude and faster velocity in this model [31,32]. In fact, the primary wave was found propagating through the entire cortex but the following waves might bypass some area of the cortex in experiments [18,[26][27][28].…”

Section: Temporal Evolution Of Repetitive Csd Wavesmentioning

confidence: 99%

“…However, the temporal variation of propagation patterns of successive CSD waves in the same region could not be entirely accounted by the cytoarchitecture. In fact, the modulation of the refractory period of CSD was found involved in the variation [31][32][33]. Both the experimental and theoretical work addressed the mechanisms of gap junctions, glial cells (astrocytes) and ion channels.…”

Section: Introductionmentioning

confidence: 99%

“…Both the experimental and theoretical work addressed the mechanisms of gap junctions, glial cells (astrocytes) and ion channels. The simulation results revealed the refractoriness conditions of CSD (i.e., the slowly inactivating inward currents overcome the outward ones) [32,34]. In order to bridge the gap between the macroscopic and microscopic level of CSD, this study paid more attention to study the variation of CSD patterns under long-lasting and transient stimulation conditions.…”

Section: Introductionmentioning

confidence: 99%

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Variation of repetitive cortical spreading depression waves is related with relative refractory period: a computational study

Chen

et al. 2015

Quant. Biol.

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Cortical spreading depression (CSD) is an important experimental model for diseases such as stroke, epilepsy and migraine. Previous observations indicated that the amplitude and velocity of the typical direct current potential shift during repetitive CSD waves were varying. The recovery state of the tissue was found related with the variation of successive CSD waves. A computational model in this paper aimed to investigate the role of relative refractory period of CSD. This model simulated that continuous injection of KCl solution induced repetitive CSD waves. The first CSD wave often had a larger amplitude and faster velocity than those of the succeeding secondary waves. The relative refractory period lasted much longer than the recovery of ions turbulence. If the induction interval was long enough for recovery, a series of CSD waves would have the same profile as the first one. In the relative refractory period, an early stimulation might lead to a late initiation of CSD, i.e., "haste makes waste". The amplitude and velocity of CSD waves were found increasing with the initiation interval and asymptotic to those of the first CSD wave. This study verified that the propagation dynamics of CSD waves is modulated by the relative refractory period. It suggested that the refractory period is critical for preventing undesirable CSD waves.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Temporal Evolution Of Repetitive Csd Wavesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Variation of repetitive cortical spreading depression waves is related with relative refractory period: a computational study

Chen

et al. 2015

Quant. Biol.

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The role of extracellular potassium dynamics in the different stages of ictal bursting and spreading depression: A computational study

Florence

Dahlem

Almeida

et al. 2009

Journal of Theoretical Biology

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Experimental evidences point out the participation of nonsynaptic mechanisms (e.g., fluctuations in extracellular ions) in epileptiform bursting and spreading depression (SD). During these abnormal oscillatory patterns, it is observed an increase of extracellular potassium concentration [K(+)](o) and a decrease of extracellular calcium concentration [Ca(2+)](o) which raises the neuronal excitability. However, whether the high [K(+)](o) triggers and propagates these abnormal neuronal activities or plays a secondary role into this process is unclear. To better understand the influence of extracellular potassium dynamics in these oscillatory patterns, the experimental conditions of high [K(+)](o) and zero [Ca(2+)](o) were replicated in an extended Golomb model where we added important regulatory mechanisms of ion concentration as Na(+)-K(+) pump, ion diffusion and glial buffering. Within these conditions, simulations of the cell model exhibit seizure-like discharges (ictal bursting). The SD was elicited by the interruption of the Na(+)-K(+) pump activity, mimicking the effect of cellular hypoxia (an experimental protocol to elicit SD, the hypoxia-induced SD). We used the bifurcation theory and the fast-slow method to analyze the interference of K(+) dynamics in the cellular excitability. This analysis indicates that the system loses its stability at a high [K(+)](o), transiting to an elevated state of neuronal excitability. Effects of high [K(+)](o) are observed in different stages of ictal bursting and SD. In the initial stage, the increase of [K(+)](o) creates favorable conditions to trigger both oscillatory patterns. During the neuronal activity, a continuous growth of [K(+)](o) by outward K(+) flow depresses K(+) currents in a positive feedback way. At the last stage, due to the depression of K(+) currents, the Na(+)-K(+) pump is the main mechanism in the end of neuronal activity. Thus, this work suggests that [K(+)](o) dynamics may play a fundamental role in these abnormal oscillatory patterns.

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Realistic spiking neural network: Non-synaptic mechanisms improve convergence in cell assembly

et al. 2020

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Identifying essential conditions for refractoriness of Leão's spreading depression—Computational modeling

Cited by 5 publications

References 24 publications

Variation of repetitive cortical spreading depression waves is related with relative refractory period: a computational study

Variation of repetitive cortical spreading depression waves is related with relative refractory period: a computational study

The role of extracellular potassium dynamics in the different stages of ictal bursting and spreading depression: A computational study

Realistic spiking neural network: Non-synaptic mechanisms improve convergence in cell assembly

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