title: Antiepileptogenic and neuroprotective effects of losartan in kainate model of temporal lobe epilepsy.
abstract: Recently, we have shown that the blockade of AT1 receptor might be useful as an adjuvant treatment strategy for the prevention of oxidative stress and neurotoxicity caused by status epilepticus (SE) in rats. The purpose of the present study was to further assess the efficacy of long-term treatment with losartan (10mg/kg), the selective AT1 receptor antagonist, during kainate (KA)-induced epileptogenesis in Wistar rats. Losartan treatment started after onset of SE and continued for 4weeks. The rats were video- and EEG-recorded for 3months. Locomotor activity, anxiety and depressive-like behavior were evaluated 9weeks after SE, when all rats had developed chronic epileptic state. Neuronal damage in hippocampus was analyzed by hematoxylin while serotonin (5-HT) levels in hippocampus by HPLC. AT1 receptor antagonism increased the latent seizure-free period and decreased the frequency of spontaneous motor seizures. Losartan positively affected epilepsy-provoked behavioral changes, including impulsivity, low anxiety level and depression in a phase-dependent manner and restored the changes in diurnal fluctuation of motor activity. Losartan exerted neuroprotection selectively in the CA1 area of the hippocampus in the KA-treated rats and lowered the 5-HT levels both in normal and abnormal conditions. Our findings suggest that the AT1 receptor antagonist exerts disease-modifying effects during KA-induced epileptogenesis and neuronal damage in CA1 hippocampal area, attenuated some of the behavioral changes and restored diurnal variability in locomotor activity.
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. Electronic address: janetchekalarova@gmail.com.
authors.forename: Jana D
authors.initials: JD
authors.lastname: Tchekalarova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Ivanova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Pechlivanova
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Dimitrina
authors.initials: D
authors.lastname: Atanasova
authors.affiliation: Department of Anatomy, Medical Faculty, MU-Sofia, Bulgaria.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Lazarov
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Lidia
authors.initials: L
authors.lastname: Kortenska
authors.affiliation: Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Mitreva
authors.affiliation: Department of Medical Chemistry and Biochemistry, Medical Faculty, MU-Sofia, Bulgaria.
authors.forename: Valentin
authors.initials: V
authors.lastname: Lozanov
authors.affiliation: Department of Pathophysiology, Medical Faculty, MU-Sofia, Bulgaria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stoynev
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000188:drug therapy*; D007608:Kainic Acid / Q000633:toxicity*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000927:Anticonvulsants; D018696:Neuroprotective Agents; D019808:Losartan; D007608:Kainic Acid
keywords: AT(1) receptor antagonism; Anxiety; Depression; Epileptogenesis; Kainate; Serotonin