Pentylenetetrazole-Induced Kindling Mouse Model

Pentylenetetrazole (PTZ) is a GABA-A receptor antagonist. An intraperitoneal injection of PTZ into an animal induces an acute, severe seizure at a high dose, whereas sequential injections of a subconvulsive dose have been used for the development of chemical kindling, an epilepsy model. A single low...

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Bibliographic Details
Published in:Journal of visualized experiments no. 136
Main Authors: Shimada, Tadayuki, Yamagata, Kanato
Format: Journal Article
Language:English
Published: United States MyJove Corporation 12.06.2018
Subjects:
animal models
animals
antagonists
brain
chronic diseases
drugs
epilepsy
gamma-aminobutyric acid receptors
genes
histology
intraperitoneal injection
neurons
Neuroscience
pathophysiology
patients
screening
seizures
ISSN:1940-087X, 1940-087X
Online Access:Get full text
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Summary:Pentylenetetrazole (PTZ) is a GABA-A receptor antagonist. An intraperitoneal injection of PTZ into an animal induces an acute, severe seizure at a high dose, whereas sequential injections of a subconvulsive dose have been used for the development of chemical kindling, an epilepsy model. A single low-dose injection of PTZ induces a mild seizure without convulsion. However, repetitive low-dose injections of PTZ decrease the threshold to evoke a convulsive seizure. Finally, continuous low-dose administration of PTZ induces a severe tonic-clonic seizure. This method is simple and widely applicable to investigate the pathophysiology of epilepsy, which is defined as a chronic disease that involves repetitive seizures. This chemical kindling protocol causes repetitive seizures in animals. With this method, vulnerability to PTZ-mediated seizures or the degree of aggravation of epileptic seizures was estimated. These advantages have led to the use of this method for screening anti-epileptic drugs and epilepsy-related genes. In addition, this method has been used to investigate neuronal damage after epileptic seizures because the histological changes observed in the brains of epileptic patients also appear in the brains of chemical-kindled animals. Thus, this protocol is useful for conveniently producing animal models of epilepsy.
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Correspondence to: Tadayuki Shimada at shimada-td@igakuken.or.jp, Kanato Yamagata at yamagata-kn@igakuken.or.jp
ISSN:1940-087X
1940-087X
DOI:10.3791/56573