Simultaneous Kindling of the Bilateral Hippocampi: An Advanced Model for Epilepsy Research

Kogure, Shinichi; Kitayama, Masaomi; Matsuda, Yoshiki

doi:10.1111/j.1528-1157.2000.tb00274.x

Cited by 8 publications

(9 citation statements)

References 21 publications

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“…Since its first descriptions over 20 years ago this phenomenon has been examined for the potential underlying mechanisms as the observation is almost counterintuitive, that seizures from one site would suppress seizures from another. Some factors have become clear: norepinephrine can play a role in modulating antagonism, that antagonism is protocol and site specific and that it may not occur in all species (Applegate et al, 1986; Teskey et al, 1999; Kogure et al, 2000; Matsuda et al, 2003). Does the observation have relevance for human epilepsy?…”

Section: Kindling To Spontaneous Seizuresmentioning

confidence: 99%

The Relevance of Kindling for Human Epilepsy

2007

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Summary:Kindling is one of the most widely used models of seizures and epilepsy, and it has been used in its more than three decade history to provide many key insights into seizures and epilepsy. It remains a mainstay of epilepsy related research, but the question remains how the results from kindling experiments further our understanding of the underlying neurobiology of human epilepsy. In this article we compare the basic features of kindling and human epilepsy, especially human limbic or temporal lobe epilepsy. In this review we focus on a limited number of topics that may show areas in which kindling has been often cited as a tool for better understanding of human epilepsy. These areas include the underlying circuits, the importance of seizure spontaneity, the associated neuropathology, the contribution of genetics, seizure susceptibility, and the underlying pathophysiology of epilepsy. In the course of this article we will show that there are many features that kindling can teach us by direct comparison or implication about human temporal epilepsy. We will also see that not all findings associated with kindling may be applicable to the human condition. Ultimately we wish to encourage critical thinking about kindling and the similarities that it shares and does not share with the human epilepsy so the results from studies using this model are applied rationally to further our insights the mechanisms of human epilepsy. Key Words: Kindling-Epilepsy-Animal models of human disease.This first paragraph is a disclaimer. One should be wary of articles and authors that start with disclaimers. What follows is a very personal view of kindling and what it can teach us about human epilepsy. The article starts philosophically from the perspective of human epilepsy and its neurobiology, based on the idea that we use models of human disorders to understand the mechanisms of the disorder that we cannot study directly in people. The logic then follows that to understand the human condition, the model ideally must have identical features. If the features are not identical, then, before one draws conclusions from the model, one must be very specific about how exactly the two states match and how they differ. Otherwise one risks the potential of drawing conclusions that may be inappropriate for the clinical situation. It is in this light that this article is written. It is highly selective in the issues discussed, and no doubt somewhat biased in its presentation. But it is based on some thought of what are some of the issues that are important in understanding human epilepsy, and then using those issues to compare reality to the model. The reader will no doubt notice the limited topics as well as the relatively sparse referencing, especially for a subject that has been researched as much as this one. There are no doubts some readers who will object significantly to some of the conclusions that are drawn, and "intense" discussions may ensue. Those objections are a good thing, because it is the ferment of scientific disagreement...

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Section: Kindling To Spontaneous Seizuresmentioning

confidence: 99%

The Relevance of Kindling for Human Epilepsy

2007

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“…The R-A was used for stimulating as well as injecting. The stimulus train for PADs was 1-ms pulses of 50 Hz for 1 s (30,31,34,35). In preliminary experiments, electrical stimuli <100 A could hardly produce paroxysmal discharges.…”

Section: Stimulation and Injectionmentioning

confidence: 99%

“…We have previously reported that the hippocampal interneuron showed a long-lasting burst discharge before the initiation of spontaneous seizure discharge in the short-term experiment using kindled rabbits, and that the apical dendrites of pyramidal cells exhibited an abnormal active property during kindling (30)(31)(32). Taking our data and several characteristics of Ih channels into consideration, we hypothesized that an anomalous hyperpolarization generates an abnormal excitation by way of Ih channels.…”

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confidence: 99%

Ih Blockers Have a Potential of Antiepileptic Effects

et al. 2003

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Summary:Purpose: The h current (Ih) is an inwardly mixed cationic conductance activated by membrane hyperpolarization and distributed predominantly in the apical dendrites of hippocampal pyramidal neurons. To verify a hypothesis that an anomalous hyperpolarization generates an abnormal excitation by way of Ih channels, we examined the effects of Ih blockers (CsCl and ZD7288) on electrically induced paroxysmal discharges (PADs).Methods: Fifty-three adult male rabbits were used. We measured the PAD threshold elicited by stimulation to the apical dendritic layer of the hippocampal CA1 region before and after injecting 50 l of each Ih blocker or saline extracellularly into the same region.Results: In Ih blocker injection groups (n ‫ס‬ 26), we obtained a significant increase in PAD threshold (1 mM CsCl: 163%, p < 0.01; 10 mM CsCl: 265%, p < 0.01; 100 mM CsCl: 199%, p < 0.01; 100 M ZD7288: 192%, p < 0.05; 1 mM ZD7288: 246%, p < 0.05). Conversely, we did not obtain the increase in PAD threshold in a saline injection group (n ‫ס‬ 10, 107%). The magnitude as well as duration of the effect had a tendency to depend on concentration of Ih blockers, although a saturated or declining tendency was observed with the 100 mM CsCl injection.Conclusions: We concluded that Ih channels might contribute to hippocampal epileptiform discharges in vivo. Our hypothesis for epileptogenesis demonstrated in the present experiment offers an idea to develop a new type of antiepileptic drug based on Ih blockers for the treatment of epileptic disorders refractory to current medications. Key Words: EpilepsyHippocampus-Paroxysmal discharge-Hyperpolarizationactivated current-In vivo physiology.Multiple ionic channels regulate neuronal activity. In the hippocampal CA1 region, Na + and Ca 2+ channels activate and inactivate neuronal membrane depolarizations and contribute to the generation of excitatory postsynaptic potentials (1-3). Before as well as after the membrane excitation, the release of ␥-aminobutyric acid from inhibitory interneurons induces inhibitory postsynaptic potentials (IPSPs) and suppresses/terminates the depolarizing potentials (4-6). Previous hypotheses for epileptogenesis were based on imbalance between such excitatory and inhibitory currents (7).Recently the h current (Ih) has been investigated (8-24), and the following characteristics of Ih were reported: (a) Ih is a voltage-gated nonselective cationic conductance activated by membrane hyperpolarization, not by depolarization (8,14); (b) Ih is blocked by cesium chloride (CsCl) or 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride (ZD7288) instead of tetrodotoxin (8,13,15); and (c) Ih channels occur in higher density in the apical dendrites than in the soma (8,14). In spite of many in vitro reports on Ih channels (8-24) as well as in vivo studies on the pacemaking function of Ih (25-28), any contributions of Ih to epileptic activity are unknown in vivo, except for the one that showed the long-lasting enhancement of the widely expressed intrinsic Ih that converts...

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“…Kindling is a canonical model used for the study of epileptogenesis, yet it receives increasing criticism due to the lack of SRS. However, over-electrical kindling ultimately results in SRS ( Kogure et al, 2000 ; McIntyre et al, 2002 ). Recent research revealed eight day consecutive flurothyl-kindling is sufficient to elicit SRS immediately after kindling, which remits weeks later ( Kadiyala et al, 2016 ).…”

Section: Srs In Rodent Models Of Epilepsymentioning

confidence: 99%

自发性癫痫在啮齿类实验动物中的模型和探测

Dalton

2017

Zool. Res.

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Epilepsy, characterized by spontaneous recurrent seizures (SRS), is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. While much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.

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Simultaneous Kindling of the Bilateral Hippocampi: An Advanced Model for Epilepsy Research

Cited by 8 publications

References 21 publications

The Relevance of Kindling for Human Epilepsy

The Relevance of Kindling for Human Epilepsy

Ih Blockers Have a Potential of Antiepileptic Effects

自发性癫痫在啮齿类实验动物中的模型和探测

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