Epileptogenesis Induced by Alternate‐site Kindling in Bilateral Hippocampi

Matsuda, Yoshiki; Yano, Masayuki; Kitayama, Masaomi; Kogure, Shinichi; Yamauchi, Takeshi

doi:10.1046/j.1528-1157.2003.25802.x

Cited by 3 publications

(1 citation statement)

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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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