The angiotensin II type I receptor antagonist losartan retards amygdala kindling-induced epileptogenesis
| Autor: | Toshiki Nozaki, Shiro Kobayashi, Hiroyuki Ura, Ichiro Takumi, Eiichi Maru, Akio Morita |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pharmacology Epileptogenesis Losartan Receptor Angiotensin Type 1 03 medical and health sciences Epilepsy chemistry.chemical_compound 0302 clinical medicine medicine Kindling Neurologic Animals Rats Wistar Molecular Biology Evans Blue Cerebral Cortex business.industry General Neuroscience Angiotensin II Antagonist medicine.disease Amygdala Extravasation 030104 developmental biology medicine.anatomical_structure chemistry Cerebral cortex Brain Injuries cardiovascular system Neurology (clinical) business Angiotensin II Type 1 Receptor Blockers 030217 neurology & neurosurgery Developmental Biology medicine.drug |
| Zdroj: | Brain research. 1694 |
| ISSN: | 1872-6240 |
| Popis: | Blood-brain barrier (BBB) breakdown and the subsequent exposure of the cerebral cortex to serum albumin are known to activate transforming growth factor β (TGF-β) signaling in astrocytes and to play key roles in epileptogenesis after brain injury. It was recently reported that the angiotensin II type I receptor antagonist losartan suppresses activation of TGF-β signaling and prevents epileptogenesis in a rat vascular injury model. Here, we investigated the effects of losartan on epileptogenesis following amygdala kindling in rats. Systemic or intracerebroventricular (i.c.v.) administration of losartan significantly delayed the development of severe behavioral seizures and stimulus-induced seizures on EEG (afterdischarge) in the early stage of amygdala kindling, as assessed by electroencephalography. Losartan also significantly increased the number of stimulations required to reach the fully kindled state. However, losartan had no effects on the threshold for afterdischarge induction, the afterdischarge duration, or seizure severity in fully kindled rats. Evaluation of BBB permeability by Evans blue staining did not indicate BBB breakdown (extravasation of serum albumin) in any region of the brain in the fully kindled animals. Thus, losartan may be useful in preventing epileptogenesis, even in post brain-insult epilepsy, in the absence of BBB breakdown. |
| Databáze: | OpenAIRE |
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