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Regional Accumulation of 14C-zonisamide in Rat Brain during Kainic Acid-induced Limbic Seizures

Published online by Cambridge University Press:  02 December 2014

Koichi Akaike ,
Shigeya Tanaka ,
Hideshi Tojo ,
Shin-ichiro Fukumoto ,
Morikuni Takigawa  and
Shin-ichi Imamura
Koichi Akaike
Affiliation:
Department of Neuropsychiatry, University of Kagoshima, Faculty of Medicine, Kagoshima, Japan
Shigeya Tanaka
Affiliation:
Department of Neuropsychiatry, University of Kagoshima, Faculty of Medicine, Kagoshima, Japan
Hideshi Tojo
Affiliation:
Department of Neuropsychiatry, University of Kagoshima, Faculty of Medicine, Kagoshima, Japan
Shin-ichiro Fukumoto
Affiliation:
Department of Neuropsychiatry, University of Kagoshima, Faculty of Medicine, Kagoshima, Japan
Morikuni Takigawa
Affiliation:
Department of Neuropsychiatry, University of Kagoshima, Faculty of Medicine, Kagoshima, Japan
Shin-ichi Imamura
Affiliation:
Department of Neurosurgery, University of Kagoshima, Faculty of Medicine, Kagoshima, Japan
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Abstract

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Background:

Zonisamide (ZNS) is an antiepileptic drug developed in Japan. Various experimental studies have investigated the effects of ZNS. However, the mechanism of action of ZNS against limbic seizures and secondary generalization is not well-known. We studied ictal regional accumulation of ZNS in the rat brain during kainic acid (KA)-induced limbic status epilepticus.

Methods:

Fourteen male Wistar rats underwent a stereotactic operation. For recording the electroencephalogram (EEG), electrodes were placed in the left amygdala (LA), left dorsal hippocampus, and over the left sensorimotor cortex. For microinjection, a stainless steel cannula was also inserted into the LA. Seven days after surgery, rats were anesthetized and a catheter was inserted into the femoral vein. The animals were immobilized and allowed to recover from anesthesia for at least two hours. In eight rats, 1.0μL (1.0μg) of KA was injected into the LA, and 1.0 μL of phosphate buffer solution was injected into the LA in six control rats. Sixty minutes after injection, 14C-ZNS was administered intravenously, and an autoradiographic study was done.

Results:

During limbic status epilepticus, only seizures in the sensorimotor cortex were markedly attenuated a few minutes after 14C-ZNS administration. Additionally, high uptake of 14C-ZNS was noted ipsilaterally in the sensorimotor cortex, parietal cortex and thalamus (lateral portion). In control rats, no EEG change was seen, and distribution of 14C-ZNS was rather homogeneous.

Conclusion:

These results suggested that ZNS suppresses secondary generalization of limbic seizures by a direct effect on the cerebral cortex.

Résumé:

RÉSUMÉ:

Accumulation régionale de zonisamide-C" dans le cerveau de rat pendant des convulsions limbiques induites par l'acide kaïque.

Introduction:

Le zonisamide (ZNS) est un antiépileptique qui a été développé au Japon. Plusieurs études expérimentales ont investigué les effets du ZNS, mais le mécanisme d'action du ZNS contre les convulsions limbiques et la généralisation secondaire demeure mal connu. Nous avons étudié l'accumulation ictale régionale de ZNS dans le cerveau de rats chez qui on a induit un status épilepticus au moyen de l'acide kaïque (AK).

Méthodes:

Quatorze rats Wistar mâles ont subi une chirurgie stéréotaxique. Pour l'enregistrement électroencéphalographique (ÉEG), les électrodes ont été placées dans l'amygdale gauche (AG), l'hippocampe dorsal gauche et le cortex sensitivomoteur gauche. Une canule d'acier inoxydable a été insérée dans l'AG. Sept jours après l'intervention, les rats ont été anesthésiés et un cathéter a été inséré dans la veine fémorale. Les animaux ont été immobilisés et on les a laissés se remettre de l'anesthésie pendant au moins deux heures. Chez huit rats, 1.0 μL (1.0 μg) d'AK a été injecté dans l'AG et 1.0 μL de solution tampon au phosphate a été injecté dans l'AG chez six rats contrôles. Soixante minutes après l'injection, le ZNS-C4 a été administré par voie intraveineuse et une étude autoradiographique a été effectuée.

Résultats:

Pendant le status épileptius limbique, seules les crises situées dans le cortex sensitivomoteur ont été atténuées de façon importante quelques minutes après l'administration du ZNS-C14. De plus, une captation élevée du ZNS-C-4 a été notée dans le cortex sensitivomoteur, le cortex pariétal et le thalamus (portion latérale) ipsilatéral. Chez les rats contrôles, aucun changement ÉEG n'a été observé et la distribution du ZNS-C-4 était plutôt homogène.

Conclusions:

Ces résultats suggèrent que le ZNS supprime la généralisation secondaire des crises convulsives limbiques par un effet direct sur le cortex cérébral.

Type
Experimental Neurosciences
Information
Canadian Journal of Neurological Sciences , Volume 28 , Issue 4 , November 2001 , pp. 341 - 345
Copyright
Copyright © The Canadian Journal of Neurological 2001

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