Stress within the postseizure time window inhibits seizure recurrence.
Recurrence is a key characteristic in the development of epilepsy. It remains unclear whether seizure recurrence is sensitive to postseizure stress. Here, tonic-clonic seizures were induced with a convulsive dose of pentylenetetrazole (PTZ), and acute seizure recurrence was evoked with a subconvulsive dose of the drug. We found that stress inhibited seizure recurrence when applied 30minutes or 2hours, but not 4hours, after the tonic-clonic seizure. The time-dependent anti-recurrence effect of stress was mimicked by the stress hormone corticosterone and blocked by co-administration of mineralocorticoid and glucocorticoid receptor antagonists. Furthermore, in a PTZ-induced epileptic kindling model, corticosterone administered 30minutes after each seizure decreased the extent of seizures both during the kindling establishment and in the following challenge test. These results provide novel insights into both the mechanisms of and therapeutic strategies for epilepsy.
Zhou
Qi-Xin
QX
Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
Mao
Rong-Rong
RR
Duan
Ting-Ting
TT
Tan
Ji-Wei
JW
Tian
Meng
M
Cao
Jun
J
Xu
Lin
L
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000927:Anticonvulsants / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006727:Hormone Antagonists / Q000627:therapeutic use; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D015735:Mifepristone / Q000627:therapeutic use; D010433:Pentylenetetrazole / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D055502:Secondary Prevention; D012640:Seizures / Q000139:chemically induced / Q000628:therapy*; D013148:Spironolactone / Q000627:therapeutic use; D013312:Stress, Physiological / Q000502:physiology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D006727:Hormone Antagonists; D013148:Spironolactone; D015735:Mifepristone; D003345:Corticosterone; D010433:Pentylenetetrazole